Method of treating early breast cancer with ribociclib in combination with an aromatase inhibitor

Abstract

The present disclosure relates to the adjuvant treatment of HR+ / HER2- stage II or III early breast cancer in adult patients. The method includes administering ribociclib (a CDK4 / 6 inhibitor) in combination with endocrine therapy.

Description

[0001] PAT059494-WO-PCT METHOD OF TREATING EARLY BREAST CANCER BACKGROUND OF THE INVENTION Breast cancer (BC) is the most frequently diagnosed cancer worldwide. Approximately 1.7 million new cases of BC and 522,000 deaths attributed to this disease were estimated to occur in 2012 worldwide (CA Cancer J Clin 65:87–108, 2015). BC incidence varies between individuals of different ethnicities and in different geographic locations around the world, with rates ranging from 27 per 100,000 in Middle Africa and Eastern Asia to 92 in Northern America (GLOBOCAN: Estimated Cancer Incidence, Mortality and Prevalence Worldwide 2012 [Internet][cited 2018 Jun 26], https: / / publications.iarc.fr / Databases / Iarc- Cancerbases / GLOBOCAN-2012-Estimated-Cancer-Incidence-Mortality-And-Prevalence- Worldwide-In-2012-V1.0-2012). In the United States, BC was projected to be the most common cancer diagnosed in 2018 with an estimated incidence of 268,670 new cases and 41,400 deaths (CA Cancer J Clin 68:7–30, 2018). Estimated incidence of BC in European countries in 2012 was 458,337 (Eur J Cancer Oxf Engl 199049:1374–1403, 2013). BC in men is not common, with a reported frequency of approximately 1% of all BC but its incidence is continuously rising (Breast Cancer Res Treat 137:465–470, 2013). The vast majority of newly diagnosed BC cases are early breast cancers (EBC), localized to the breast tissue and regional lymphatics, which are potentially treatable with locoregional treatment modalities such as surgery and radiation therapy. Based on Surveillance, Epidemiology and End Results (SEER) Program data collected between the years 1975 and 2012, 93% of cases diagnosed were EBC, with 62% limited to the breast tissue and 31% localized within the breast tissue and regional lymph nodes (SEER Cancer Statistics Review, 1975-2015 [Internet]. Bethesda, MD, National Cancer Institute, 2018, https: / / seer.cancer.gov / csr / 1975_2015 / ). Besides primary surgery, management of EBC usually includes additional anti-neoplastic treatment modalities such as radiation therapy and adjuvant or neoadjuvant systemic therapy. Although many patients with EBC may be rendered disease-free with surgical resection and radiotherapy, distant recurrence due to micro-metastatic disease is common and is the primary cause of death in patients with EBC (BMC Med 13:195, 2015). According to the EBC Trialists’ Collaborative Group (EBCTCG) meta-analysis of almost 150,000 women in 200 randomized clinical trials, approximately 36% and 20% of patients with EBC without any adjuvant systemic therapy will experience recurrence and death due to BC, respectively, during 5 years of follow- up (Lancet Lond Engl 365:1687–1717, 2005). Moreover, recurrences and BC-related deaths in patients with hormone receptor (HR)-positive EBC continue to occur after 5 years from surgery, with only 45% of patients reported to be recurrence-free at 15 years of follow-up. PAT059494-WO-PCT Adjuvant systemic treatments that comprise cytotoxic, biological and endocrine therapies in patients with EBC decrease locoregional and distant recurrences, decrease BC-specific mortality and improve overall survival (OS) (Lancet Lond Engl 365:1687–1717, 2005). The need and selection of systemic adjuvant therapies is based on individual risk of recurrence and may be guided by several clinical, pathological and genomic predictive and prognostic factors of tumor and patient such as tumor stage, histopathological grade, tumor HR status, human epidermal growth factor receptor-2 (HER2) status, multi-gene testing recurrence scores, proliferation markers like Ki67, menopausal status, patient’s comorbidities, age, and others. Using these factors, EBC can be classified as having low, intermediate / moderate or high risk for recurrence after surgery (BMC Med 13:195, 2015). While there is no consensus on the definition of these risk groups, generally, patients with smaller tumors, no metastasis in regional lymph nodes, low tumor grade, HR-positive and HER2-negative status, and low recurrence genomic score have low risk of recurrence (i.e.5-10% recurrences at 5-years). These patients are usually considered for adjuvant endocrine therapy (ET), without chemotherapy, due to a lower clinical benefit of latter versus the former. On the other hand, patients with metastases in multiple regional lymph nodes, high tumor grade, HER2-positive status or high recurrence genomic score have a higher risk of recurrence. These patients are usually considered for adjuvant chemotherapy (and HER2 targeting agents in patients with HER2-positive BC), and if the tumor expresses HR, adjuvant ET is considered too (normally delivered after the completion of chemotherapy). It is estimated that 75% of BC express receptors for steroid hormones (estrogen receptor [ER] and / or progesterone receptor [PgR]), and therefore these patients may benefit from adjuvant ET with tamoxifen or aromatase inhibitors (AIs) (letrozole, anastrozole, or exemestane) (J Clin Oncol Off J Am Soc Clin Oncol 28:2784–2795, 2010). ET, independent of chemotherapy, reduces the risk of recurrence and BC deaths in HR-positive EBC (Lancet Lond Engl 365:1687– 1717, 2005). Current clinical guidelines (see Ann Oncol Off J Eur Soc Med Oncol 26 Suppl 5:v8-30, 2015; and National Comprehensive Cancer Network. Breast Cancer (Version 1.2019) [Internet]. NCCN , 2019 [cited 2019 May 6], https: / / www.nccn.org / professionals / physician_gls / pdf / breast.pdf) for adjuvant ET in the HR- positive EBC recommend: • For premenopausal women: 1.1. 5-10 years of tamoxifen with or without ovarian suppression, or 1.2. 5 years of AI with ovarian suppression (see N Engl J Med 379:122–137, 2018) • For postmenopausal women: PAT059494-WO-PCT 1.3. Initial AI for 5 years (or up to 10 years), based on results from the MA.17R trial (see N Engl J Med 375:209–219, 2016), or 1.4. Initial tamoxifen for 2-3 years followed by AI either up to total 5 years, or up to 5 years of treatment with AI, or 1.5. Tamoxifen for ~5 years followed by 5 years of AI, or 1.6. Tamoxifen up to 10 years (Ann Oncol Off J Eur Soc Med Oncol 26 Suppl 5:v8- 30, 2015; National Comprehensive Cancer Network. Breast Cancer (Version 1.2019) [Internet]. NCCN , 2019 [cited 2019 May 6], https: / / www.nccn.org / professionals / physician_gls / pdf / breast.pdf) • In men: Limited data suggest that tamoxifen or the combination of an AI with a gonadotropin-releasing hormone (GnRH) agonist should be the ET of choice for HR- positive, HER2-negative EBC (Breast Cancer Res Treat 151:141–147, 2015). WO2015 / 022609 A1, incorporated herein by reference, discloses combination therapies for the treatment of cancer, including EBC. In some EBC patients, recurrences may still occur, especially in patients with adverse clinical, pathological, and genomic features. Approximately 25%-30% of patients with HR-positive, HER2-negative EBC with multiple (≥4) metastatic regional lymph nodes (largely corresponding to Anatomic Stage Group III in the AJCC 8thedition Breast Cancer Staging) will recur within 5 years with ET that includes AIs (Lancet Lond Engl 365:1687–1717, 2005). Only 48% of these patients will be distant recurrence-free within 20 years, with almost half of patients dying of BC within 20 years, despite ET for 5 years (N Engl J Med 377:1836–1846, 2017). While patients with 1-3 metastatic regional lymph nodes (corresponding generally to Anatomic Stage Group II in the AJCC 8thedition Breast Cancer Staging) may have lower risk of recurrence than patients with Anatomic Stage Group III, still 31% of them will experience distant recurrence and 28% will die from BC within 20 years despite ET (N Engl J Med 377:1836–1846, 2017). Adjuvant treatments for HR+ HER2- EBC remain limited. Although adjuvant treatments similar to those used in patients with HR+ HER2- advanced or metastatic breast cancer have been tried, results obtained from that approach have been variable. In one example, the cdk4 / 6 inhibitor abemaciclib was first approved for treatment of patients with HR+ HER2- advanced or metastatic breast cancer either alone or in combination with endocrine therapy, and was later shown in the monarchE clinical trial to be efficacious in treatment of patients with HR+ HER2- high risk early breast cancer (Johnston et al., 2023. Lancet 24(1), pp.77-90). In contrast, the cdk4 / 6 inhibitor palbociclib combined with endocrine therapy demonstrated clinically relevant efficacy in patients with HR+ HER2- metastatic breast cancer (PALOMA3 trial, described in Turner et al., 2015. N Engl J Med 2015; 373:209-219), but the results did not bear out in trials in PAT059494-WO-PCT patients with HR+ HER2- early breast cancer (see the PENELOPE-B trial, where adding palbociclib to endocrine therapy in patients having HR+ HER2- early breast cancer and residual invasive disease after completing neoadjuvant chemotherapy did not improve invasive disease free survival (iFDS) as compared to placebo control when added to ET therapy (Loibl et al., 2021. Breast Cancer v39(14)). Similarly, results from the PALLAS clinical trial in patients with HR+ HER2- early-stage breast cancer indicated that combination of palbociclib with endocrine therapy did not improve iDFS when compared with endocrine therapy alone (Mayer et al., 2021. Lancet, v22 (2), p212-222). Therefore, new therapeutic strategies may improve clinical outcomes in patients with HR- positive, HER2-negative EBC. SUMMARY OF THE INVENTION Accordingly, disclosed herein are methods of treating early breast cancer using the CDK4 / 6 inhibitor Kisqali® (ribociclib) plus endocrine therapy (ET). The present disclosure provides methods of treatment for patients with hormone receptor-positive / human epidermal growth factor receptor 2-negative (HR+ / HER2-) early breast cancer (EBC). The disclosure relies, inter alia, on the results from the NATALEE trial, a positive Phase III study of a CDK4 / 6 inhibitor demonstrating consistent benefit in a broad population of patients with stage II and III HR+ / HER2- early breast cancer (EBC) at risk of recurrence, including those with no nodal involvement. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1 provides a schematic of the study design of the NATALEE clinical trial. FIG.2 shows simulated ANC Mean Profiles at Ribociclib 200 mg, 400 mg, and 600 mg QD, 3 weeks on / 1 week off; mean ANC profiles are predicted by the ANC exposure-response model developed based on data from studies CLEE011X2101, CLEE011X1101, CLEE011X2107, CLEE011A2301, CLEE011E2301 and CLEE011F2301. FIG.3 provides a schematic of the inclusion according to anatomic stage group in the NATALEE clinical trial. FIG.4 provides a schematic of ECG and PK Relative to Dosing (C1D15). FIG.5 illustrates a questionnaire (i.e., EORTC QLQ-C30) for use, for example, of assessment of quality of life and healthcare resources utilization. FIG.6 illustrates a questionnaire (i.e., EORTC QLQ-BR23) for use, for example, of assessment of quality of life and healthcare resources utilization. FIG.7 illustrates a questionnaire (i.e., EQ-5D-5L) for use, for example, of assessment of quality of life and healthcare resources utilization. FIG.8 illustrates a questionnaire (i.e., Hospital Anxiety Depression Scale (HADS)) for use, for example, of assessment of quality of life and healthcare resources utilization. PAT059494-WO-PCT FIG.9 shows a Kaplan-Meier Plot (Full analysis set) for the Primary Invasive Disease-Free Survival Analysis. FIG.10 shows a (q) Forest Plot of iDFS by stratum (per eCRF) (Full analysis set). FIG.11A shows a Forest Plot of iDFS – subgroup analysis. FIG.11B shows a Forest Plot of iDFS – subgroup analysis. FIG.11C shows a Forest Plot of iDFS – subgroup analysis. FIG.11D shows a Forest Plot of iDFS – subgroup analysis. FIG.12 shows iDFS - Kaplan-Meier survival curves of iDFS by Anatomic Stage II (eCRF stratum) (Full analysis set). FIG.13 shows iDFS - Kaplan-Meier survival curves of iDFS by Anatomic Stage III (eCRF stratum) (Full analysis set). FIG.14 shows Kaplan-Meier curves for RFS (Full analysis set). FIG.15 shows Kaplan-Meier curves for DDFS (Full analysis set). FIG.16 shows Kaplan-Meier curves for OS (Full analysis set). DETAILED DESCRIPTION OF THE INVENTION Herein after, the present disclosure is described in further detail and is exemplified. The present disclosure relates to methods for treating patients suffering from breast cancer (BC). The methods are based, inter alia, on surprising results from the NATALEE clinical trial which indicate that a combination of a CDK inhibitor plus endocrine therapy can provide beneficial effects in patients with early breast cancer, for example, an early breast cancer that is hormone receptor-positive / human epidermal growth factor receptor 2-negative (HR+ / HER2-). A. Treatment of early breast cancer One aspect of the present disclosure relates to a method of treatment for breast cancer in an adult patient in need thereof, comprising administering to the patient a treatment comprising a cyclin-dependent kinase (CDK) inhibitor in combination with endocrine therapy, wherein the breast cancer is early breast cancer (EBC). EBCs may be characterized by localization of cancer cells (e.g., forming a tumor) in the breast tissue and regional lymphatics. In EBC, cancer cells are typically not detected beyond the breast or the axillary lymph nodes. Early breast cancer may be stage 0, stage I, stage II, or stage III cancer (e.g., stage 0, stage I, stage IIA, stage IIB, stage IIIA, stage IIIB, or stage IIIC). Due to its localization, EBC may be differentiated from advanced breast cancer (also called metastatic cancer) where the cancer has spread to one or more parts of body, such as the bones, lungs, liver, etc. PAT059494-WO-PCT In some embodiments, the EBC is a carcinoma of the breast, such as an adenocarcinoma. The EBC may be an invasive carcinoma. Invasive carcinomas, also known as infiltrating or invasive ductal carcinomas (IDC), are a type of breast cancer that starts in the milk ducts of the breast and moves into nearby tissue. In time, IDC may spread (metastasize) through the lymph nodes or bloodstream to other areas of the body. The EBC may be a noninvasive carcinoma, such as a ductal carcinoma in situ (DCIS) of the breast. The DCIS may have spread along the milk duct in the breast, but not outside of the duct system. Signs and / or symptoms of early breast cancer may be one or more of a lump in the breast or armpit, thickening or swelling of part of the breast, irritation or dimpling of breast skin (e.g., dimpling that resembles an orange peel), redness or flaky skin in the nipple area of the breast, pulling in the nipple or pain in the nipple area, nipple discharge other than breast milk, including blood, any change in the size or shape of the breast, and / or pain in any area of the breast. Additional signs and / or symptoms of early breast cancer may comprise the presence of a breast cancer cell or cells, the presence of a breast cancer tumor, or the presence of biochemical or genetic markers in a patient’s tissues or body fluids which indicate that the presence of breast cancer (e.g., breast cancer biomarkers in a tissue biopsy or a blood sample). The presence may be a physical presence, detected using tests such as ultrasound, mammogram, magnetic resonance imaging, analysis of tissue samples (e.g., a biopsy) and / or analysis of samples of body fluids (e.g., a blood sample). Any known test may be used for detecting signs and / or symptoms of cancer. The term “No evidence of disease” (NED or NEOD) may be used when there is no detectable sign and / or symptom of a cancer. Breast cancers may be graded according to their histology. A histologic grade (or “grade”) may refer to the extent that a cancer cell differs from a normal cell, for example, by differing in the degree of cell differentiation. Grade 1 refers to breast cancer cells that resemble normal breast cells and are usually slow growing. Grade 2 refers to breast cancer cells that may not resemble normal breast cells and grow fast. Grade 3 refers to breast cancer cells that do not resemble normal breast cells and are usually fast growing. Grade 4 refers to breast cancer cells that least resemble normal breast cells and tend to grow and spread faster than lower grade tumors. Breast cancers may be categorized according to a staging method. A staging method may be a pathologic staging method, e.g., based on a pathologist’s study of the tumor tissue and any lymph nodes removed during surgery, or a clinical staging method, e.g., based on a clinician’s physical exam, tests, and / or imaging. In general, staging methods are used to categorize breast cancers based on the size of the cancer (e.g., a primary tumor) and how far the cancer has spread in the body. PAT059494-WO-PCT One method used to categorize breast cancers or tumors based on their stage is the TNM classification or staging method. Using this method, a tumor may be classified as T0 when there is no evidence of a tumor, while classifications of T1, T2, T3, or T4 may be used for to identify the size and extension of the tumor. Tx may indicate that the tumor cannot be assessed. N (node) describes the spread of cancer to nearby lymph nodes. A tumor may be classified as N0 when there is no spread of the tumor to regional nodes, while classifications of N1-N3 may be used to indicate nodal spread. M (metastasis) describes metastasis (e.g., spread of cancer to other parts of the body). A tumor may be classified as M0 when no distant metastasis is present, while a classification of M1 may be used when there is evidence of distant metastasis (Rosen and Sapra, TNM Classification, StatPearls Publishing; Treasure Island (FL), January 2023). In breast cancer, T1 may be defined as a tumor 20 mm or less in diameter. T1a may be defined as a tumor more than 1 mm but not more than 5 mm in greatest dimension; T1b may be defined as a tumor more than 5 mm but not more than 10 mm in greatest dimension; T1c may be defined as a tumor more than 10 mm but not more than 20 mm in greatest dimension. T2 may be defined as a tumor more than 20 mm but not more than 50 mm in greatest dimension. T3 may be defined as a tumor more than 50 mm in greatest dimension. T4 may be defined as a tumor of any size with direct extension to the chest wall and / or the skin (e.g., ulceration or skin nodules). T4a may be extension to the chest wall. T4b may be defined as edema of the skin or ulceration of the skin of the breast, or satellite skin nodules confined to the same breast. T4c may be defined as both T4a and T4b. T4d may be defined as inflammatory cancer, e.g., cancer characterized by diffuse erythema and edema involving approximately a third or more of the skin of the breast. Regional lymph nodes near the breast may comprise one or more of (1) axillary lymph nodes, the interpectoral (Rotter’s nodes), and lymph nodes along the axillary vein and its tributaries. Axillary lymph nodes may be Level I (low-axilla), Level II (mid-axilla), or Level III (apical axilla); (2) internal mammary lymph nodes; (3) superclavical lymph nodes; and (4) intramammary lymph nodes. For cancers that have or can spread to the lymph nodes, N0 indicates that the cancer has not spread to nearby lymph nodes; N1 indicates that the cancer has spread to 1 to 3 axillary lymph nodes, and / or is found in internal mammary lymph nodes on sentinel lymph node biopsy; N2 indicates that the cancer has spread to 4 to 9 axillary lymph nodes, or has enlarged the internal mammary lymph nodes; and N3 indicates that the cancer has spread to 10 or more axillary lymph nodes, with at least one area of cancer spread greater than 2 mm, or has spread to infraclavicular nodes, with at least one area of cancer spread greater than 2 mm, or is found in at least one axillary lymph node (with at least one area of cancer spread greater than 2 mm) PAT059494-WO-PCT and has enlarged the internal mammary lymph nodes, or has spread to 4 or more axillary lymph nodes (with at least one area of cancer spread greater than 2 mm), and to the internal mammary lymph nodes on sentinel lymph node biopsy, or has spread to the supraclavicular nodes on the same side of the cancer with at least one area of cancer spread greater than 2 mm. Node categorization may be a clinical categorization or may be a pathological categorization. Clinical categorization may comprise cN1 defined as metastasis in ipsilateral level I, II axillary lymph nodes; cN2a defined as metastasis in ipsilateral level I, II axillary lymph nodes fixed to one another (matted); cN2b defined as metastasis only in clinically detected ipsilateral internal mammary nodes and in the absence of clinically evident level I, II axillary lymph node metastasis; cN3a defined as metastasis in ipsilateral infraclavicular (level III axillary) lymph nodes with our without level I, II axillary lymph node involvement; cN3b defined as metastasis in clinically detected ipsilateral internal mammary lymph node(s) and clinically evident axillary lymph node(s); or cN3c defined as metastasis in ipsilateral superclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement. An add-on to the TMN classification system is the R classification system, or residual tumor classification system, which may be used to indicate the tumor status following treatment. The R classification may indicate the effects of treatment and may be used to predict prognosis. For example, a patient may be diagnosed with a tumor that is classified using the TMN classification system and then treated, after which any residual tumor may be classified according to the R classification system. Using this system, the extent of resection of a tumor can is classified as R0, R1, or R2. In R0, there is no residual tumor after surgery, e.g., the surgical margin is microscopically negative for residual tumor. In R1, there is no residual macroscopic tumor but microscopic margins still demonstrate the presence of tumor. In R2, the gross (macroscopically- visible) tumor remains post-surgery. The TNM classification system predates many genetic tests and / or biochemical marker (or “biomarker”) tests that are now routinely used to provide additional predictive or prognostic information about cancer types, and may be used together with these and / or other tests for categorizing cancers. For example, the TNM classification system may be used in combination with measures such as tumor grade, estrogen receptor (ER) status, progesterone receptor (PR) status, and human epidermal growth factor receptor 2 (HER2) status. An example of such a combination is provided in Table 1 of Ann Surg Oncol.2018 Jul;25(7):1783-1785. doi: 10.1245 / s10434-018-6486-6. Epub 2018 Apr 18. One example of a biomarker used in breast cancer is the nuclear antigen Ki-67. Ki-67 levels may be measured in breast cancer cells, for example, using immunohistochemical staining. The anti-human Ki-67 antibody MIB1 may be used for the immunohistochemistry. Ki-67 values are PAT059494-WO-PCT calculated as a percentage of positively marking malignant cells among the total number of malignant cells assessed (Breast Cancer Res Treat.2013; 139(2): 539–552). In general, Ki-67 expression correlates with high levels of cell proliferation (J Clin Oncol.2005 Oct 1;23(28):7212- 20). Genetic tests such as multigene or multiparameter expression assays may be used to evaluate characteristics of a breast cancer, risk of metastasis, and / or risk of recurrence. One exemplary test is the Oncotype DX® test, where a breast recurrence score of ≥ 26 (on a scale of 0-100) indicates a risk for recurrence. In another exemplary test, the Prosigna® / PAM50 (Prediction Analysis of Microarray 50) test, tumors are assigned a score of low risk, intermediate risk, or high risk for metastasis, depending on the expression levels of 50 genes in the tumor. Other exemplary tests include but are not limited to the MammaPrint®, EndoPredict®, and Breast Cancer Index® tests, which may be used to determine risk scores for cancer recurrence. Another method for categorizing tumors is the “Stage Grouping” categorization system. This method, which may be used alone or together with the TNM classification system and other tests, groups breast cancers in Anatomic Stage Groups (or “stages”). Thus, breast cancer may be categorized according to a stage group (or “Anatomic Stage Group”) 0, I, II, III, or IV. In particular, the stage group may be stage 0, Ia, Ib, IIa, IIb, IIIa, IIIb, IIIC, or IV. Stage 0: Stage zero (0) may describe disease that is only in the ducts of the breast tissue and has not spread to the surrounding tissue of the breast. It is also called non-invasive or in situ cancer (Tis, N0, M0). Stage IA may refer to a tumor that is small, invasive, and has not spread to the lymph nodes (T1, N0, M0). Stage IB may refer to cancer that has spread to the lymph nodes and the cancer in the lymph node is larger than 0.2 mm but less than 2 mm in size. There may be either no evidence of a tumor in the breast or the tumor in the breast is 20 mm or smaller (T0 or T1, N1mi (also called “N1 micrometastatic”), M0). Stage IIA may refer to cancer meeting any one of these conditions: a. There is no evidence of a tumor in the breast, but the cancer has spread to 1 to 3 axillary lymph nodes. It has not spread to distant parts of the body (T0, N1, M0). b. The tumor is 20 mm or smaller and has spread to 1 to 3 axillary lymph nodes (T1, N1, M0). c. The tumor is larger than 20 mm but not larger than 50 mm and has not spread to the axillary lymph nodes (T2, N0, M0). PAT059494-WO-PCT Stage IIB may refer to either of these conditions: a. The tumor is larger than 20 mm but not larger than 50 mm and has spread to 1 to 3 axillary lymph nodes (T2, N1, M0). b. The tumor is larger than 50 mm but has not spread to the axillary lymph nodes (T3, N0, M0). Stage IIIA may refer to a tumor of any size that has spread to 4 to 9 axillary lymph nodes or to internal mammary lymph nodes. It has not spread to other parts of the body (T0, T1, T2, or T3; N2; M0). Stage IIIA may also be a tumor larger than 50 mm that has spread to 1 to 3 axillary lymph nodes (T3, N1, M0). Stage IIIB may refer to a tumor that has spread to the chest wall or caused swelling or ulceration of the breast, or it is diagnosed as inflammatory breast cancer. It may or may not have spread to up to 9 axillary or internal mammary lymph nodes. It has not spread to other parts of the body (T4; N0, N1, or N2; M0). Stage IIIC may refer to a tumor of any size that has spread to 10 or more axillary lymph nodes, the internal mammary lymph nodes, and / or the lymph nodes under the collarbone. It has not spread to other parts of the body (any T, N3, M0). Stage IV (metastatic) may refer to a tumor that can be any size and has spread to other organs, such as the bones, lungs, brain, liver, distant lymph nodes, or chest wall (any T, any N, M1). Metastatic cancer found when the cancer is first diagnosed occurs about 6% of the time. This may be called de novo metastatic breast cancer. Most commonly, metastatic breast cancer is found after a previous diagnosis of early-stage breast cancer. Recurrent cancer is cancer that has come back after a treatment and can be described as local, regional, and / or distant (Breast Cancer: Stages, from Cancer.Net). Recurrence may be evaluated by medical imaging and confirmed histologically (or cytologically, when applicable). Recurrences may be classified into local, regional, or distant recurrence, or contralateral invasive breast cancer or second primary non-breast invasive cancer according to the following guidelines: - Local invasive breast cancer recurrence or ipsilateral invasive breast tumor recurrence: invasive breast cancer involving the same breast as the original primary tumor. Ductal and lobular carcinoma in situ and tumors in the contralateral breast and / or contralateral lymph nodes are not considered a local invasive recurrence. May be confirmed histologically. PAT059494-WO-PCT - Regional breast cancer recurrence: invasive breast cancer in the ipsilateral axilla, regional lymph nodes (all levels), chest wall, or skin of the ipsilateral breast. A tumor in the contralateral breast is not considered a regional recurrence. May be confirmed histologically (preferred) or cytologically. - Distant recurrence: distant metastasis of breast cancer (bones, distant lymph nodes, internal organs, CNS, bone marrow, etc.) or any areas of invasive breast cancer recurrence that are not local or regional. Distant recurrence may be confirmed histologically (preferred) or cytologically. o If bone metastases were identified by a bone scan, it may be confirmed histologically (preferred) or radiographically (CT, MRI, or FDG-PET-CT) if biopsy confirmation is not possible. o Metastases in the central nervous system may be confirmed histologically (preferred), cytologically, or radiographically (CT or MRI, both with IV contrast) if biopsy confirmation is not possible. o All other sites of metastases may be confirmed histologically (preferred) or cytologically unless there is an unacceptable risk to the patient due to the procedure. - Contralateral invasive breast cancer: any invasive breast cancer in the contralateral breast with or without contralateral lymph nodes involvement. Contralateral invasive breast cancer has to be confirmed histologically. In situ / non-invasive contralateral breast cancers are not included in contralateral invasive breast cancers. - Second primary non-breast invasive cancer: any second primary non-breast invasive cancers. Second primary non-breast invasive cancer has to be confirmed histologically. In situ / non-invasive cancers and basal or squamous cell carcinomas of the skin are not considered as second primary non-breast invasive cancers. Table B1 summarizes Anatomic Stage Groups from the AJCC 8thEdition Table B1 Anatomic Stage T-category N-category Group 0 Tis N0 PAT059494-WO-PCT IB T0-1 N1mi IIA T0-1 N1 IV T1-T3 N1-N3 Note that T2, T3, and T4 tumors with nodal micrometastases (N1mi) may be staged using the N1 category. Accordingly, in some embodiments, the adult patient treated with the methods herein has an EBC that is a ductal carcinoma in situ, a stage I breast cancer, a stage II breast cancer such as a IIA breast cancer or a stage IIB breast cancer, or a stage III breast cancer such as a stage IIIA, a stage IIIB, or a stage IIIC breast cancer. In some embodiments, the patient has a stage II or III early breast cancer. In some embodiments, the patient has a stage IIA cancer or a stage IIB cancer. In some embodiments, the patient has a stage IIIA cancer, a stage IIIB cancer, or a stage IIIC cancer. The patient may be node-positive (e.g., cancer has spread to their lymph nodes) or node-negative (e.g., cancer has not spread to their lymph nodes). In some embodiments, the treatment methods as described herein are performed irrespective of the nodal status of the patient’s breast cancer. In certain embodiments, the EBC is a hormone receptor-positive (HR+) breast cancer, e.g., a breast cancer comprising cells expressing one or more type of hormone receptor. Exemplary hormone receptors may be estrogen receptors (ERs), such as ERα or ERβ, and / or progesterone receptors (PRs) such as PRA and PRB. EBCs may comprise breast cancer cells expressing either estrogen receptors (ER+) or progesterone receptors (PR+), or a combination of both estrogen receptors and progesterone receptors (ER+ / PR+). In some embodiments, the EBC is ER+ / PR-, ER- / PR+, or ER+ / PR+. PAT059494-WO-PCT In certain embodiments, the EBC is positive for human epidermal growth factor receptor 2 (HER2). Certain embodiments relate to a method of preventing or reducing signs or symptoms of early stage breast cancer, comprising administering to the patient a treatment comprising ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof in combination with an aromatase inhibitor, preferably letrozole or anastrozole. In some embodiments, the ribociclib is a freebase form thereof or a pharmaceutically acceptable salt thereof, and is administered to the patient in a dose ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle. In some embodiments, the aromatase inhibitor is administered on every day of the 28-day cycle. B. CDK Inhibitors and Endocrine Therapy One aspect of the present disclosure relates to a method of treatment for early breast cancer in an adult patient in need thereof, comprising administering to the patient a treatment comprising a cyclin-dependent kinase (CDK) inhibitor in combination with endocrine therapy (ET). Cyclin-dependent kinases (CDKs) are serine / threonine protein kinases that bind to cyclins to form an active complex in cells. In healthy cells, various extra- and intra-cellular cues closely regulate the formation of the CDK / cyclin complex and control its phosphorylation of target proteins involved in the cell cycle, such as retinoblastoma (Rb) proteins, lamins, histone H 1, and components of the mitotic spindle. In cancer cells, however, CDKs can become hyperactivated, leading to uncontrolled tumor proliferation. CDK4 and CDK6, which bind to D-cyclins, are exemplary CDKs that have been shown to promote growth of certain breast cancer tumors. In these tumors, D-cyclins are overexpressed, leading to activation of CDK4 and CDK6, subsequently, to phosphorylation of Rb, release of Rb’s suppression of the E2F transcription factor, and rapid progression of tumor cells through the cell cycle (Shah et al., Oncology.2018 May 15; 32(5): 216–222). CDK inhibitors have been shown to block the unregulated cell growth and division resulting from hyperactivation of CDKs and / or overexpression of cyclin proteins. For example, inhibitors of CDK / cyclin complexes, and of CDK4 / 6 in particular, have been used for treating patients suffering from certain types of cancer. CDK4 / 6 inhibitors palbociclib, ribociclib, and abemaciclib have been approved by regulatory authorities for treatment of advanced or metastatic breast cancer that is hormone receptor positive (HR+ or HR-positive), and human epidermal growth factor receptor 2 negative (HER2-) (Fassi et al., Science.2022 Jan 14; 375(6577): eabc1495). To date, ribociclib has been approved by a number of regulatory authorities including the United States Food and Drug Administration (FDA) and the European Commission. By the FDA it has PAT059494-WO-PCT been approved in combination with: (1) an AI for the treatment of pre / perimenopausal or postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine-based therapy; or (2) fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine based therapy or following disease progression on ET. In Europe, ribociclib is indicated for the treatment of women with HR-positive, HER2-negative locally advanced or metastatic breast cancer in combination with an AI or fulvestrant as initial endocrine-based therapy, or in women who have received prior ET. In pre- or perimenopausal women, the ET may be combined with a luteinizing hormone-releasing hormone agonist. Accordingly, in some embodiments of the present disclosure, the CDK inhibitor used in the methods disclosed herein may be a CDK4 / 6 inhibitor, for example, an inhibitor of a CDK4 / 6 / cyclin complex. The cyclin may be a D cyclin, such as cyclin-D1 in a CDK4 / cyclin-D1 complex or cyclin-D3 in a CDK6 / cyclin-D3 complex. In some embodiments, the CDK4 / 6 inhibitor may be a compound described by Formula A1 below or a salt thereof. The compound of Formula A1 is known by the international non-proprietary name ribociclib. Thus, in some embodiments, the CDK4 / 6 inhibitor may be a compound having the international non-proprietary name ribociclib. Ribociclib may be in the form of its free base or may be a pharmaceutically acceptable salt of ribociclib. Salts can be present alone or in mixture with free compound, e.g. ribociclib, and are preferably pharmaceutically acceptable salts. Such salts of ribociclib are formed, for example, as acid addition salts, preferably with organic or inorganic acids, from compounds of ribociclib with a basic nitrogen atom. Suitable inorganic acids are, for example, halogen acids, such as hydrochloric acid, sulfuric acid, or phosphoric acid. Suitable organic acids are, e.g., succinic acid, carboxylic acids, or sulfonic acids, such as fumaric acid or methansulfonic acid. For isolation or purification purposes it is also possible to use pharmaceutically unacceptable salts, PAT059494-WO-PCT for example picrates or perchlorates. For therapeutic use, only pharmaceutically acceptable salts or free compounds are employed (where applicable in the form of pharmaceutical preparations), and these are therefore preferred. In some embodiments, ribociclib may be in the form of racemates, diastereoisomers, enantiomers, and tautomers, as well as the corresponding crystal modifications where present, e.g. solvates, hydrates, and polymorphs. Ribociclib may be in the form of a pharmaceutically acceptable salt, for example, a succinic acid salt such as ribociclib succinate. The chemical name of ribociclib succinate is butanedioic acid— 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine- 6-carboxamide (1:1) corresponding to the molecular formula C27H36N8O5. It has a relative molecular mass of 552.6 g / mol (EMA Assessment report for Kisqali, Procedure No. EMEA / H / C / 004213 / 0000, dated June 22, 2017). Oral tablet forms of ribociclib are known in the art (e.g. WO2016 / 166703) and have been approved as the KISQALI® product. Various ribociclib salts have been described (e.g. see claim 85 of WO2022 / 207788), and the approved KISQALI® product contains ribociclib succinate. Quantities of any salt will be adjusted to provide the desired quantity of ribociclib (e.g.254.40mg of ribociclib succinate corresponds to 200mg of ribociclib). Various polymorphs of ribociclib succinate are known (e.g. see WO2019 / 040567, WO2019 / 082143, WO2019 / 150181, WO2019 / 166987, WO2020 / 225827, WO2021 / 038590, etc.). The methods described herein may be implemented using the approved KISQALI® product, e.g., along with approved endocrine therapies. As described herein, the CDK inhibitor (e.g, a CDK4 / 6 inhibitor such as ribociclib or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) may be administered with endocrine therapy. In some embodiments of the present disclosure, the endocrine therapy is an aromatase inhibitor. Endocrine therapy (also called hormone therapy, hormonal therapy, or hormone treatment) has been used to slow or stop the growth of hormone-sensitive cancers (also called hormone- dependent cancers). Hormone-sensitive tumors express receptors for hormones such as estrogen and / or progesterone, and the hormones may promote growth of the cancer. Accordingly, endocrine therapy refers to a therapy that either (1) interferes with the effects of the hormones on the cancer cells and / or (2) blocks the body’s ability to produce hormones. Exemplary compounds that interfere with the effects of hormones on breast cancer cells are selective estrogen receptor modulators (SERMs), which bind to estrogen receptors and prevent estrogen from binding. SERMs may mimic the effects of estrogen. SERMs approved by the FDA for treatment of breast cancer are tamoxifen (Nolvadex®) and toremifene (Fareston®). Other PAT059494-WO-PCT anti-estrogen drugs may bind to estrogen receptors without mimicking the effects of estrogen, and may instead target the estrogen receptor for destruction. An exemplary anti-estrogen compound is fulvestrant (Faslodex®). The production of hormones may be blocked by ablating tissues or organs that produce the hormones. In premenopausal women, for example, where the ovaries are the main source of estrogen, ovarian ablation (e.g., by oophorectomy (also called ovariotomy or ovariectomy) or treatment with radiation) may be performed to remove or reduce estrogen levels. Alternatively, the production of hormones may be blocked by administering compounds that suppress synthesis and / or release of the hormones. Gonadotropin-releasing hormone (GnRH) agonists administered over a prolonged period may cause desensitization and consequently suppression of gonadotropin secretion. GnRH antagonists, in contrast, inhibit GnRH signal transduction and gonadotropin secretion (Reprod Biomed Online.2002;5 Suppl 1:1-7. doi: 10.1016 / s1472-6483(11)60210-1). Exemplary GnRH agonists are goserelin (Zoladex®) and leuprolide (Lupron®), which suppress release of estrogen from the ovaries in women and suppress the release of testosterone from the testicles in men. In some embodiments, goserelin is used in the methods disclosed herein. A further class of compounds that block production of estrogen, in particular, are aromatase inhibitors. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens in a process called aromatization. Notably, in premenopausal women, the ovaries produce levels of aromatase that are too high to be blocked by aromatase inhibitors alone. For premenopausal women, aromatase inhibitors may be combined with a compound that suppresses ovarian function (e.g., goserelin or leuprolide). In contrast, postmenopausal women produce estrogen primarily in peripheral tissues and not in the ovaries, so aromatase inhibitors may be sufficient to inhibit production of estrogen in these women. There are two types of aromatase inhibitors: (1) steroidal inhibitors, such as exemestane (Aromasin®) which forms a permanent and deactivating bond with the aromatase enzyme; and (2) non-steroidal inhibitors (NSAIs), such as anastrozole (Arimidex®) or letrozole (Femara®). Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system. Letrozole acts by highly selective inhibition of conversion of androgens (mainly from adrenal glands, the primary source of estrogens in postmenopausal women) to estrogens. Letrozole induces a 75% to 95% decrease of estrogen levels after two weeks of treatment with daily doses of 0.1 to 5 mg, with no significant clinical and laboratory toxicities or changes in levels of other hormones of the endocrine system (Lancet Lond Engl 386:1341–1352, 2015; Cancer 75:2132–2138, 1995). PAT059494-WO-PCT Anastrozole, like letrozole, is a selective NSAI. It significantly lowers serum estradiol concentrations with no detectable effect on formation of adrenal corticosteroids or aldosterone. In some embodiments, the endocrine therapy administered with the CDK inhibitor (e.g, a CDK4 / 6 inhibitor such as ribociclib or a pharmaceutically acceptable salt thereof such as ribociclib succinate) is an aromatase inhibitor, e.g., anastrozole or letrozole. In some embodiments, the therapy further comprises a gonadotropin-releasing hormone agonist such as goserelin. Exemplary aromatase inhibitors are described in Breast Cancer Res Treat.2007 Oct; 105(Suppl 1): 7–17. The aromatase inhibitor may be a non-steroidal aromatase inhibitor described by one of the formulas below, or a pharmaceutically acceptable salt thereof. Formula (C1) PAT059494-WO-PCT In some embodiments, the aromatase inhibitor may be letrozole. The aromatase inhibitor may be a pharmaceutically acceptable salt of letrozole. The chemical name of letrozole is 4,4'-(1H- 1,2,4-Triazol-1-ylmethylene)dibenzonitrile. Letrozole may be freely soluble in dichloromethane, slightly soluble in ethanol, and practically insoluble in water. It has a molecular weight of 285.31 g / mol, empirical formula C17H11N5, and a melting range of 184°C to 185°C. In some embodiments, letrozole may be in the form of racemates, diastereoisomers, enantiomers, or tautomers, as well as the corresponding crystal modifications where present, e.g. solvates, hydrates and polymorphs. In some embodiments, the aromatase inhibitor may be anastrozole or a pharmaceutically acceptable salt thereof. The chemical name of anastrozole is α,α,α',α'-tetramethyl-5-(1H-1,2,4- triazol-1-ylmethyl)-m-benzenediacetonitrile. Anastrozole is freely soluble in methanol, acetone, ethanol, and tetrahydrofuran, and very soluble in acetonitrile. It has a molecular weight of 293.374 g / mol, empirical formula C17H19N5, and a melting range of 80°C to 86°C. In some embodiments, anastrozole may be in the form of a solvate, hydrate or polymorph. In some embodiments, endocrine therapy may comprise an aromatase inhibitor (such as letrozole or anastrozole) for postmenopausal women. For premenopausal women or men, the endocrine therapy may comprise an aromatase inhibitor (such as letrozole or anastrozole) and PAT059494-WO-PCT may further comprise a compound that suppresses gonadal function (e.g., a GnRH agonist such as goserelin). The GnRH agonist may be a compound according to the formula below or a pharmaceutically acceptable salt thereof: Formula (F1) In some embodiments, the aromatase inhibitor may be goserelin or a pharmaceutically acceptable salt thereof. Goserelin is sold under the tradename Zoladex®. It has a molecular weight of 1269.433 g / mol, and an empirical formula C59H84N18O14. In some embodiments, goserelin may be in the form of a solvate, hydrate or polymorph. C. Administration - Doses and Treatment Schedule A further aspect of the present disclosure relates to a method of treatment for early breast cancer in an adult patient in need thereof, comprising administering to the patient a treatment comprising a dose of a cyclin-dependent kinase (CDK) inhibitor, in combination with a dose of an endocrine therapy. In some embodiments, the CDK inhibitor is a CDK4 / 6 inhibitor such as ribociclib or a pharmaceutically acceptable salt thereof (such as ribociclib succinate) and the endocrine therapy is an aromatase inhibitor such as letrozole. In some embodiments, the endocrine therapy is letrozole. Ribociclib at a dose of 600 mg daily from days 1 to 21 of a 28-day cycle has been shown to be tolerable and efficacious when combined with ET in clinical trials in patients with advanced BC (N Engl J Med 375:1738–1748, 2016). However, due to the potential for later recurrence of HR- positive, HER2-negative EBC, where events may occur from a year after surgery and lasting for at least 15 years after diagnosis, a longer duration of therapy may also be beneficial for EBC. In some embodiments, ribociclib (in combination with ET) may be administered at a dose of less than 600 mg daily. For example, ribociclib (or a pharmaceutically acceptable salt thereof such PAT059494-WO-PCT as ribociclib succinate) may be administered at a dose of about 400 mg daily. This exemplary dose may be administered as 2 x 200 mg daily. In some embodiments, the ribociclib (or a pharmaceutically acceptable salt thereof such as ribociclib succinate) may be administered at dose of about 400 mg / day. The dose of ribociclib or a pharmaceutically acceptable salt thereof (such as ribociclib succinate) may be administered once per day in a tablet form, for example, as 2 x 200 mg tablets (it being understood that these two tablets may be taken simultaneously or sequentially within the single daily dosing). The dose may be administered as an oral solution. The dose may be administered orally (by mouth). In some embodiments, the dose of the ribociclib or a pharmaceutically acceptable salt thereof (such as ribociclib succinate) is about 200 mg / day. This dose may be administered in a tablet form, for example, as 1 x 200 mg tablet. The dose may be administered orally (by mouth). The dose may be a flat fixed dose, e.g., not calculated by body weight or body surface area. A dose adjustment may be made, for example, to administer a dose of ribociclib or a pharmaceutically acceptable salt thereof (such as ribociclib succinate) that is less than about 400 mg / day. For example, a dose of about 350 mg / day, about 300 mg / day, about 250 mg / day, about 200 mg / day, or about 150 mg / day of ribociclib or a pharmaceutically acceptable salt thereof (such as ribociclib succinate) may be administered. In some embodiments, a dose of about 200 mg / day is administered after an earlier dose of 400 mg / day has been administered. In some embodiments, the dose is administered in tablet form, such as 1 x 200 mg tablet. The dose of about 200 mg / day may be administered orally. Accordingly, a patient who had previously received a dose of about 400 mg dose of ribociclib or a pharmaceutically acceptable salt thereof (such as ribociclib succinate) (e.g., 2 x 200 mg tablets orally) may receive a dose of about 200 mg / day instead (e.g., 1 x 200 mg tablets orally). The dose may taken once daily (e.g., 1 x 200 mg tablets once daily, or 2 x 200 mg tablets once daily). The dose adjustment may be made for patients who do not tolerate a dose of about 400 mg / day. For example, patients who receive a dose of about 400 mg / day of ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) and experience one or more of thrombocytopenia, decreased absolute neutrophil count (ANC), febrile neutropenia, anemia, hepatoxicity (e.g., as indicated by bilirubin levels and / or levels of AST and ALT enzymes), drug-induced liver injury, heart abnormalities (e.g., as measured by QT interval), interstitial lung disease / pneumonitis, and / or other adverse events may receive an adjusted dose of about 200 mg / day dose of ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate). Thus, the dose of ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) may range from about 150 mg / day to about 450 mg / day. The dose may be about 150 PAT059494-WO-PCT mg / day, about 200 mg / day, about 250 mg / day, about 300 mg / day, about 350 mg / day, or about 450 mg / day. The dose may be taken once daily. In some embodiments, the dose of ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) is not about 600 mg / day. In some embodiments, the aromatase inhibitor is letrozole. The dose of letrozole may be selected according to data (e.g., clinical data) indicating disease-free survival in patients, which may be combined with data about adverse effects such as renal impairment and / or hepatic impairment, to establish an effective dose. The dose may be selected by testing efficacy and tolerance in an individual patient. The dose of letrozole may range from about 1 mg / day to about 4 mg / day. For example, the dose of letrozole may be about 1 mg / day, about 1.25 mg / day, about 1.5 mg / day, about 1.75 mg / day, about 2 mg / day, about 2.25 mg / day, about 2.5 mg / day, about 2.75 mg / day, about 3 mg / day, about 3.25 mg / day, about 3.5 mg / day, about 3.75 mg / day, or about 4 mg / day. In some embodiments, the dose of letrozole is about 2.5 mg / day. The dose may be a flat fixed dose, e.g., not calculated by body weight or body surface area. The dose of letrozole may be administered orally (e.g., by mouth). Accordingly, any of the dosages listed above, such as a dose of letrozole that is about 2.5 mg / day, may be administered. The dose of letrozole may be administered orally. The dose may be administered in tablet form. The dose may be taken once daily. In certain embodiments, the aromatase inhibitor is anastrozole. The dose of anastrozole may be selected according to data (e.g., clinical data) indicating disease-free survival in patients, which may be combined with data about adverse effects such as renal impairment and / or hepatic impairment, to establish an effective dose. The dose may be selected by testing efficacy and tolerance in an individual patient. The dose of anastrozole may range from about 0.5 mg / day to about 1.5 mg / day. For example, the dose of anastrozole may be about 0.5 mg / day, about 0.75 mg / day, about 1 mg / day, about 1.25 mg / day, or about 1.50 mg / day. In some embodiments, the dose of anastrozole is about 1 mg / day. The dose of anastrozole may be administered orally (e.g., by mouth). Accordingly, any of the dosages listed above, such as a dose of anastrozole that is about 1 mg / day may be administered. The dose of anastrozole may be administered orally. The dose may be administered in tablet form. The dose may be taken once daily. In addition to the ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) (e.g., about 400 mg / day, or about 200 mg / day) and letrozole (about 2.5 mg / day) or PAT059494-WO-PCT anastrozole (about 1 mg / day), patients may receive a gonadotropin-releasing hormone agonist such as goserelin. For example, patients who are premenopausal women and patients who are men may receive a dose of goserelin. The dose of goserelin may be selected according to data (e.g., clinical data) indicating efficacy in patients, or by testing efficacy and tolerance in an individual patient. The dose of goserelin may range from about 2 mg to about 5 mg. The dose of goserelin may be about 2 mg, about 2.25 mg, about 2.5 mg, about 2.75 mg, about 3 mg, about 3.25 mg, about 3.5 mg, about 3.75 mg, about 4 mg, about 4.25 mg, about 4.5 mg, about 4.75 mg, or about 5 mg. In some embodiments, the dose of goserelin is about 3.4 mg, 3.5 mg, 3.6 mg, or 3.7 mg. In some embodiments, the dose of goserelin is 3.6 mg. The dose may be a flat fixed dose, e.g., not calculated by body weight or body surface area. The dose of goserelin may be administered subcutaneously. The dose may be administered subcutaneously at time intervals ranging from 2 weeks to 4 weeks. In one embodiment, goserelin is administered subcutaneously at a dose of 3.6 mg. The compounds may be administered separately, for example, when the compounds are administered by different routes of administration and / or administered according to different treatment schedules. If administered separately, the compounds may be administered simultaneously, or sequentially. In one exemplary example, two compounds are administered to the patient in two separate doses, but are administered on the same day as each other. In this example, the two compounds may be administered at the same time, or they may be administered at different times. The compounds may be administered separately in two or more separate unit doses (e.g., where a unit dose is the amount of the compound administered to the patient in a single dose) and / or unit dosage forms. Compounds may be combined for administration together. Compounds may be administered together in a single pharmaceutical composition, for example, the compounds may be administered together in a single dose (e.g., a unit dose). The unit dosage form may also be a fixed combination. In some embodiments, a dose of ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) (about 400 mg / day, or about 200 mg / day) and a dose of endocrine therapy (e.g., letrozole (dose about 2.5 mg / day) or anastrozole (dose about 1 mg / day) are administered together. In general, the doses may be administered at the same time each day, such as in the morning. The doses may be administered in the afternoon or evening. In some embodiments, the doses are not administered in the evening. PAT059494-WO-PCT A further aspect of the present disclosure relates to a method of treatment for early breast cancer in an adult patient in need thereof, comprising administering to the patient a treatment comprising a dose of a cyclin-dependent kinase (CDK) inhibitor, in combination with a dose of an endocrine therapy, according to a treatment schedule. In some embodiments, the treatment schedule comprises a treatment cycle of about 28 days. In this cycle, the CDK inhibitor may be administered once daily on days 1 to 21 of the 28-day cycle, followed by 7 days off the CDK inhibitor, wherein during the off days the endocrine therapy is administered once daily continuously. Accordingly, the endocrine therapy (e.g., letrozole or anastrozole) may be administered on every day of the 28-day cycle. Accordingly, in some embodiments the CDK inhibitor is ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) administered at a dose of about 400 mg / day (or about 200 mg / day) and the endocrine therapy is letrozole administered at a dose of about 2.5 mg / day or anastrozole administered at a dose of about 1 mg / day, wherein the ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) is administered once daily on days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) (days 22-28 of the cycle), and the letrozole or anastrozole is administered once daily continuously during the 28-day period (e.g., on every day of the 28-day cycle). The ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) may be administered orally, for example, in tablet form. The letrozole or the anastrozole may be administered orally, for example, in tablet form. For patients whose treatment further comprises administration of goserelin (e.g., at a dose of about 3.6 mg), this may be administered once during the 28-day cycle. The goserelin may be administered every 2-4 weeks, for example, every 4 weeks. In some embodiments, the goserelin is administered on day 1 (± 3 days) of each 28-day cycle. The goserelin may be administered on day -3, day -2, day -1, day 1, day 2, or day 3 of the 28-day cycle. The treatment may be administered for at least about 12 months. The treatment may be administered for at least about 12 months, at least about 18 months, at least about 24 months, at least about 30 months, at least about 36 months, at least about 42 months, at least about 48 months, at least about 54 months, at least about 60 months, or longer. In some embodiments, the ribociclib and letrozole are administered for at least about 48 months (about 4 years), or at least about 60 months (about 5 years). In some embodiments, the treatment is administered for at least 36 months. An exemplary dose and treatment schedule is shown in Table B1.1. Table B1.1. Exemplary dose and treatment schedule PAT059494-WO-PCT Trial Treatment Pharmaceutical form and Dose Frequency and / or Regimen route of administration Ribociclib Tablets for oral use 400 mg Once daily on days 1 to 21 in each (LEE011200 mg) 28-day cycle Letrozole 2.5 mg Tablets for oral use 2.5 mg Once daily given continuously Anastrozole 1 mg Tablets for oral use 1 mg Once daily given continuously Goserelin 3.6 mg Implant, in pre-filled 3.6 mg Day 1 ± 3 of each 28-day cycle syringe and Subcutaneous use In some embodiments, the patient has not received a loading dose prior to treatment. In some embodiments, the patient has received a loading dose prior to treatment. For example, the patient may have received a loading dose of ribociclib (e.g., or a ribociclib salt such as ribociclib succinate) and / or an endocrine therapy (e.g, letrozole or anastrozole). A loading dose may be an initial dose of a drug that may be given at or prior to the beginning of a course of treatment before dropping down to a different, typically lower dose (e.g., a treatment or maintenance dose). A loading dose may be a single dose or short duration regimen of a compound which is administered to the subject to rapidly increase the blood concentration level of the drug. Suitably, a short duration regimen for use herein will be from: 1 to 14 days; e.g., from 1 to 7 days; e.g., from 1 to 3 days; e.g., for three days; e.g., for two days; e.g., for one day. In some embodiments, the “loading dose” can increase the blood concentration of the drug to a therapeutically effective level. In some embodiments, the “loading dose” can increase the blood concentration of the drug to a therapeutically effective level in conjunction with a treatment dose of the drug. The “loading dose” can be administered once per day, or more than once per day (e.g., up to 4 times per day). In some embodiments, a loading dosage may be used for drug molecules that have a long half-life or slow elimination in vivo. In some embodiments, the treatment continues until the patient has no remaining signs and / or symptoms of breast cancer. In some embodiments, the treatment continues until the patient has no detectable cancer and / or no signs (e.g., indication) of cancer recurrence. In some embodiments, treatment is reinitiated if a patient exhibits one or more signs of cancer recurrence. In some embodiments, the treatment continues until the cancer recurs. Signs and / or symptoms of cancer and cancer recurrence may be determined by monitoring the patient over months and years following treatment, using tests such as physical examinations, scans and / or imaging of the site where the cancer was (e.g., x-rays, computed tomography, mammography), and blood tests. In an exemplary example, different modalities for follow up may be PAT059494-WO-PCT mammography, clinical examination, whole body or localized MRI and / or CT scans. In accordance with guidelines from the National Comprehensive Cancer Network, a breast cancer patient may have (1) medical history taken and physical exam performed 1–4 times per year as clinically appropriate for 5 years, (2) a mammography every 12 months, and (3) in the absence of clinical signs and symptoms suggestive of recurrent disease, there is no indication for laboratory or imaging studies for metastases screening. When no cancer is detected, patients may be assumed to be treated, but must be observed for recurrence of disease. In some embodiments, the treatment as disclosed herein may be administered to patients who no longer have detectable signs and / or symptoms of cancer, but who may remain at risk for recurrence of cancer. The treatment may continue in these patients for a period of time , e.g., ranging from at least about 3 months to at least about 10 years, e.g., 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, or 10 years, or any time period in between. During this time, the patient may be monitored for recurrence of cancer, for example, according to clinical examination, mammography, scans, imaging, sample collection (e.g., biopsy of tissues), and / or blood tests. A patient who does not have detectable signs and / or symptoms of cancer in the period of time may discontinue the treatment described herein. In some embodiments, a patient may continue the treatment for an additional period of time. In some embodiments, a patient whose cancer recurs may discontinue the treatment, for example, to try another treatment option. D. Patients Another aspect of the present disclosure relates to a method of treatment for early breast cancer in an adult patient in need thereof, comprising administering to the patient a treatment comprising a cyclin-dependent kinase (CDK) inhibitor, in combination with endocrine therapy, wherein the adult patient is selected or characterized according to one or more criteria. The criteria may relate to patient demographics, features of the patient’s early breast cancer (e.g., type, stage, grade, hormone-receptor status, etc.), previous treatment, and / or other criteria as described herein. I. Age In some embodiments, the patient is an adult, e.g., 18 years of age or greater. In some embodiments, the patient is about 18 years to about 45 years of age. In some embodiments, the patient is about 45 years of age to about 54 years of age. In some embodiments, the patient is about 55 years of age to about 64 years of age. In some embodiments, the patient is about 64 years of age or older. The patient may belong to an age category that is less than the median PAT059494-WO-PCT age for a given population of EBC patients, or alternatively, the patient may belong to an aged category that is greater than or equal to the median age for a population of EBC patients. II. Gender and menopausal status In some embodiments, the patient is a woman. In other embodiments, the patient is a man. For female patients, the patient’s menopausal status may be premenopausal. Alternatively, the female patient’s menopausal status may be postmenopausal. A patient with postmenopausal status may be defined as (1) a patient who underwent bilateral oophorectomy; (2) a patient having an age more than or equal to 60 years; (3) a patient having an age of less than 60 years and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression) and Follicle-stimulating hormone (FSH) and plasma estradiol in the postmenopausal ranges per local normal ranges; or (4) a patient having an age of less than 60 years old and who is taking tamoxifen or toremifene, and has FSH and plasma estradiol level in postmenopausal ranges. Premenopausal status may be defined for patients who do not meet the criteria for postmenopausal status. For women with premenopausal status, amenorrhea may not be a reliable indicator of menopausal status as ovarian function may still be intact or resume despite anovulation / amenorrhea. For these women with therapy-induced amenorrhea, serial measurements of FSH and / or estradiol per local clinical guidelines may be used for a determination of postmenopausal status. III. Child bearing potential In some embodiments, the patient is a woman of childbearing potential (CBP), defined as physiologically capable of becoming pregnant. Women may be considered of CBP unless they have had 12 months or more than 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, the woman may be considered not of CBP after confirmation by hormone level assessment. In some embodiments, the patient is a woman of CBP who is not pregnant. In some embodiments, the patient is not a pregnant or breast-feeding (lactating) woman or a woman who plans to become pregnant or breast-feed during the treatment as described herein. PAT059494-WO-PCT IV. Diagnosis of breast cancer In some embodiments, a patient in need of treatment for early breast cancer is a patient who has been diagnosed with early breast cancer. The patient may not have received a prior treatment for the early breast cancer. The patient may have received a prior treatment for the early breast cancer, such as surgery, chemotherapy, radiation therapy, and / or hormone therapy, but may still be in need of a treatment because the early breast cancer did not respond to the prior treatment. In some embodiments, the patient received a prior treatment for early breast cancer and has a recurrence of the early breast cancer. In some embodiments, the patient received a prior treatment for a cancer, but has been diagnosed with early breast cancer. In some embodiments, the patient is at risk for developing early breast cancer and / or at risk for a recurrence of early breast cancer. The patient at risk may not have detectable signs or symptoms or early breast cancer, but may be at risk due to a previous diagnosis of cancer. In some embodiments, the patient received a prior treatment for early breast cancer, such as HR+ HER2- stage II or stage III early breast cancer, and has no detectable signs or symptoms of early breast cancer, but remains at risk for recurrence of early breast cancer. Risk factors may relate to the early breast cancer for which the patient received treatment, where a high tumor grade, large tumor size (e.g., greater than 2 mm), and axillary node involvement may correlate with a higher risk for recurrence. In some embodiments, the patient has a breast cancer that is diagnosed as and / or confirmed (e.g., histologically confirmed) to be a carcinoma of the breast. The carcinoma may have been diagnosed within 18 months prior to starting treatment. The carcinoma may be a unilateral primary invasive adenocarcinoma. The carcinoma may be a multicentric and / or multifocal tumor. V. Hormone receptor (HR) status and expression of human epidermal growth factor receptor 2 (HER2) In some embodiments, the patient has breast cancer that is hormone receptor positive. The breast cancer may be positive for ER and / or PR. The breast cancer may be ER+ / PR-, ER- / PR+, or ER+ / PR+. In some embodiments, the patient has a breast cancer that is a HER2- breast cancer. For example, the breast cancer may be defined as a cancer with a negative result from an in situ hybridization test and / or an immunohistochemistry (IHC) status of 0 or 1+. If the breast cancer has an IHC of 2+, a negative in situ hybridization (FISH, CISH, or SISH) may be used to confirm HER2- status. PAT059494-WO-PCT VI. Tumor characteristics In some embodiments, the patient has a breast cancer comprising a tumor that belongs to one of the following categories: • Anatomic Stage Group III, or • Anatomic Stage Group IIB, or • Anatomic Stage Group IIA that is either: • N1, or • N0, with: • Grade 3, or • Grade 2. In some embodiments, patients having a tumor that Anatomic Stage Group IIA, N0, and Grade 2, may have additional measures to categorize the breast cancer. For example, the tumor may have a Ki67 percentage that is about 20% or greater than about 20%. The tumor may have scores in multiparameter tests that indicate a risk for recurrence and / or spread of cancer, such as a breast recurrence score of ≥ 26 (on a scale of 0-100) in the Oncotype DX® test, a high risk score in Prosigna® / PAM50 (Prediction Analysis of Microarray 50) test, a high risk score MammaPrint® test, or a high risk score EndoPredict® EPclin test. In some embodiments, the patient has a stage IIA tumor. In some embodiments, the patient has a stage IIB tumor. In some embodiments, the patient has a stage IIIA tumor. In some embodiments, the patient has a stage IIIB tumor. In some embodiments, the patient has a stage IIIC tumor. In some embodiments, the patient does not have a stage IV tumor, e.g., a breast cancer tumor with distant metastases beyond the lymph nodes. In some embodiments, the patient has a tumor with a nodal status that is selected from NX, N0, N1, N2, or N3. For example, the patient may have a tumor with N0 status. Alternatively, the patient may have a tumor with N1, N2, or N3 status, or a tumor with a status that is any one of N1, N2, or N3. In some embodiments, the patient has a tumor of category T0, category Tis, T1, T2, T3, or a category T4 tumor. In some embodiments, the patient has a tumor of category T0. The patient may have a tumor of category T1, T2, or T3 status, or a tumor that is any one of T1, T2, or T3. In some embodiments, the patient has a tumor of category T4. PAT059494-WO-PCT In some embodiments, the patient has a tumor with an M stage of M0. In some embodiments, the patient has a tumor of histological grade GX, G1, G2, or G3 (e.g., Grade X, Grade 1, Grade 2, or Grade 3). The patient may have a tumor of histological grade of Grade 1. The patient may have a tumor of histological Grade 2. The patient may have a tumor of histological Grade 3. In certain embodiments, the patient has a tumor with a Ki67 status of less than or equal to 20%. The Ki67 category may be less than or equal to 14%, or the Ki67 category may be greater than 14%. Alternatively, the patient may have a tumor with a Ki67 status of more than 20%. Ki67 may be measured in archival samples of resected tumors from the patient. Ki67 is a proliferation marker in normal and human cell populations, which may be used as a clinical marker for breast cancers and a predictive marker for success with endocrine therapy. In some embodiments, the patient has a tumor that has been evaluated by a genomic test, such as one or more of an Endopredict® test, a Mammaprint® test, an Oncotype DX® test, a Prosigna / PAM50® test, and a Breast Cancer Index® test. The patient may have a risk score from one or more tests that indicates a high risk for cancer recurrence and / or metastasis. In some embodiments, the tumor has an EndoPredict EPclin® risk score that indicates high risk. In some embodiments, the tumor has an Mammaprint® test result that indicates high risk. In some embodiments, the tumor has an Prosigna / PAM50® test result that indicates high risk. In some embodiments, the tumor has a Oncotype DX Breast Recurrence Score that is a greater than or equal to about 26. Measures such as histopathological grade, T stage, N stage, M stage, and Ki67 may be determined at the time of initial diagnosis or on a surgical specimen. In some embodiments, the patient has a tumor of a ductal subtype. The patient may have a tumor of a lobular subtype. Alternatively, the patient may have a tumor of a subtype that is neither ductal nor lobular. In some embodiments, the predominant histology of the tumor is selected from invasive ductal carcinoma, no otherwise specified (NOS), invasive lobular, carcinoma medullary, mucinous, papillary, tubular, ductal carcinoma in situ, and lobular carcinoma in situ. In some embodiments, the patient has a tumor comprising a HER2 ISH result comprising an IHC score of 0, 1+, 2+, or 3+. The HER2 ISH result may be obtained prior to surgery or from a surgical specimen. PAT059494-WO-PCT In some embodiments, the patient has a positive hormone receptor status. For example, a positive ER status and / or a positive PR status. The positive status may be obtained prior to surgery or from a surgical specimen. In certain embodiments, the patient has a tumor with no metastasis in sentinel lymph nodes (e.g., the patient is considered as pN0). The patient may have only micrometastasis in sentinel lymph nodes (e.g., the patient is considered as pN1mi). Patients may have tumors that are T1-2 and no clinically-evident nodes prior to surgery, no neoadjuvant chemotherapy, at least one macrometastasis in 1 or 2 sentinel lymph nodes, and / or no matted nodes or gross extranodal disease at the time of sentinel dissection (e.g., patient is considered as pN1). In some embodiments, staging of breast cancer is performed by lymph node dissection, such as axillary lymph node dissection (ALND). In some embodiments, staging is performed by sentinel lymph node (SLN) dissection. In some embodiments, the tumor is located in only the right breast and not the left breast. Alternatively, the tumor may be located only in the left breast and not in the right breast. In some embodiments, the tumor is bilateral, e.g., comprising cancer cells located in both the right breast and the left breast. VII. Body mass index In some embodiments, the patient has a body mass index (BMI) that is more than 25 or equal to 25. In some embodiments, the patient has a BMI that is less than 25. VIII. Prior treatment for cancer In some embodiments, the patient has received treatment (which may also be called therapy) for the breast cancer prior to undergoing the methods described herein. The prior treatment may be a primary treatment (also called a primary therapy, main treatment or therapy, induction treatment or therapy, or first-line treatment or therapy) for breast cancer. In some embodiments, the patient has completed a primary treatment for breast cancer before the treatment as described herein. Accordingly, the treatment described herein may be an adjuvant treatment following a prior treatment. In some embodiments, the prior treatment is not a primary treatment, but follows a primary treatment or other treatments. In these examples, the treatment described herein may be an adjuvant treatment to a prior treatment, wherein the prior treatment itself followed one or more additional prior treatments for breast cancer. The prior treatment may itself be an adjuvant treatment for a primary treatment. The prior treatment may be a neoadjuvant treatment for a primary treatment. The prior treatment may be PAT059494-WO-PCT a neoadjuvant treatment for the treatment disclosed herein. In some embodiments, the patient completes the prior treatment (e.g., adjuvant and / or neoadjuvant treatment) before the treatment disclosed herein. In a further exemplary example, the prior treatment is a neoadjvant treatment for a primary treatment. For example, the prior treatment may be administered to shrink a tumor before the primary treatment. In some embodiments, both the prior treatment and the primary treatment for which the prior treatment is a neoadjuvant treatment are completed before the treatment described herein. In some embodiments, the prior treatment is neoadjuvant treatment for the treatment described herein. A prior treatment may be radiotherapy (also “radiation therapy”), surgical treatment, or chemotherapy. In some embodiments, the prior treatment is radiotherapy. Radiotherapy may be located at one or more of the following: breast, chest wall, axillary lymph node, supraclavicular lymph node, and internal mammary lymph node. In some embodiments, the patient has undergone a surgical treatment. Accordingly, a prior treatment may be surgical resection of the cancer cells (e.g., tumor). For example, the patient may have had one or more of a mastectomy, a breast conserving surgery, an axillary lymph node dissection, or a sentinel lymph node biopsy. In some embodiments, the patient has had a mastectomy. In some embodiments, the patient has had a lumpectomy. In some embodiments, an entire organ or even the surrounding structures may be removed in order to achieve the necessary cancer (e.g., tumor) resection. A surrounding amount of normal, healthy tissue (called “surgical margin”) may be removed to increase the success of surgery. Accordingly, in some embodiments, the prior treatment comprises complete tumor resection. The cancer may be removed completely, with final surgical specimen microscope margins free from tumor. In some embodiments, following surgical resection, the cancer may be R0 (for example, the surgical margin is microscopically negative for residual tumor). In some embodiments, the patient is administered the treatment as described herein as an adjuvant treatment after a prior treatment of surgery. For example, the treatment described herein may start after surgical resection where the tumor was removed completely, with final surgical specimen microscopic margins free from tumor. The prior treatment may be chemotherapy. In some embodiments, the patient has received a prior treatment that is a chemotherapy. The chemotherapy may be a neoadjuvant chemotherapy. For example, the neoadjuvant chemotherapy may have been administered PAT059494-WO-PCT before another treatment such as a surgical procedure, radiation therapy, or administration of another medication. The chemotherapy may be an adjuvant chemotherapy. For example, the prior treatment may be a chemotherapy that was administered after another treatment such as a surgical procedure, radiation therapy, or administration of another medication. The chemotherapy may be a neo- / adjuvant chemotherapy. In these exemplary examples, the prior treatment (e.g., neoadjuvant chemotherapy and / or adjuvant chemotherapy) occurs before the treatment according to the methods described herein. In some embodiments, the patient has received a prior anti-neoplastic chemotherapy, for example, an anthracylcine or a taxane. In some embodiments, the patient has received endocrine therapy (ET). The ET may be, for example, a neoadjuvant and / or adjuvant ET. The patient may have received ET within 12 months of beginning the present methods. In some embodiments, the patient has received tamoxifen or toremifene as an adjuvant ET, wherein the patient undergoes a washout period of 5 half-lives (e.g., 35 days) prior to beginning the present methods. The patient may receive aromatase inhibitors during the washout period. In some embodiments, the patient has received an endocrine therapy selected from an aromatase inhibitor, an anti-estrogens, a gonadotropin-releasing hormone analogues, or and a biologic / targeted therapy. In some embodiments, the patient has undergone previous treatment, but the breast cancer did not respond to treatment, for example, due to resistance of the breast cancer cells to a drug. In some embodiments, the patient has undergone previous treatment, but the breast cancer has recurred (or “relapsed”). In some embodiments, the patient has received treatment (which may also be called therapy) for the breast cancer prior to undergoing the treatment described herein, and is in remission. The patient may be in remission from early breast cancer, for example, HR+ / HER2- early breast cancer. The HR+ / HER2- early breast cancer may be stage II or stage III cancer. A cancer may be in remission. A patient who had cancer may be in remission. In both cases, remission may refer to a decrease in or a disappearance of signs of cancer in a patient, following a treatment for cancer. Remission may be partial remission, in which a cancer (e.g., cancer cells and / or a tumor) has decreased in size or in the extent of spread in the body. For example, partial remission may reflect a 50% reduction in measurable parameters for cancer such as growth, size, or spread of cancer cells and / or a tumor. Remission may be complete remission, where signs of cancer (e.g., cancer cells and / or a tumor) are no longer detectable. In complete remission, there may be no evidence of disease. PAT059494-WO-PCT In complete remission, there may be no detectable signs or symptoms of cancer. Remission may be related to the period of time since the patient had detectable signs or symptoms of cancer. For example, after about 1 month without detectable signs or symptoms of cancer, the patient may be described as being in remission. In some embodiments, the period of time is about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 13 months, about 14 months, about 15 months, about 16 months, about 17 months, about 18 months, about 19 months, about 20 months, about 21 months, about 22 months, about 23 months, about 24 months, about 25 months, about 26 months, about 27 months, about 28 months, about 29 months, about 30 months, about 31 months, about 32 months, about 33 months, about 34 months, about 35 months, about 36 months, or longer. In some embodiments, the period of time is about 4 years, about 5 years, about 6 years, about 7 years, about 8 years, about 9 years, about 10 years, or longer. Accordingly, the treatment as described herein may be administered to patients who are in remission. In some embodiments, the patients are in complete remission. In some embodiments, the patients are in partial remission. In some embodiments, the patient is in full remission at the time that the treatment described herein begins. For example, the patient may not have detectable cancer cells and / or a tumor. The patient may have been diagnosed with early breast cancer at a previous time and may have been treated with a prior treatment, with the result that cancer is no longer detectable. Accordingly, a patient who does not have symptoms of cancer may be administered with the treatment described herein. In some embodiments, the patient may have been diagnosed with a HR+ / HER2- early breast cancer and treated with surgery to remove the cancer, and HR+ / HER2- early breast cancer may no longer be detectable. In some embodiments, the patient may be at risk for developing HR+ / HER2- breast cancer based on the presence of a HR+ / HER2- breast cancer diagnosed previously. For example, the patient may be at risk for recurrence of HR+ / HER2- breast cancer based on a previous diagnosis of HR+ / HER2- early breast cancer. In some embodiments, the patient is in partial remission and shows detectable signs of cancer at the time that the treatment described herein begins. In some embodiments, the patient was diagnosed with a HR+ / HER2- early breast cancer and treated with a prior treatment, but the cancer was not fully removed and / or the cancer recurred. In some embodiments, the patient in partial remission may be at risk for regrowth and / or spread of HR+ / HER2- breast cancer based on a previous diagnosis of HR+ / HER2- early breast cancer. PAT059494-WO-PCT In some embodiments, the treatment described herein prevents growth of HR+ / HER2- breast cancer cells in the patient, for example, a patient who is in remission (e.g., in full remission or in partial remission). In some embodiments, the treatment described herein maintains the patient in remission (e.g., in full remission or in partial remission). The treatment may maintain the remission for at least about 3 months, at least about 6 months, at least about 12 months, at least about 18 months, at least about 24 months, at least about 30 months, at least about 36 months, at least about 42 months, at least about 48 months, at least about 54 months, at least about 60 months, at least about 66 months, at least about 72 months, at least about 78 months, at least about 84 months, at least about 90 months, at least about 96 months, at least about 102 months, at least about 108 months, at least about 114 months, at least about 120 months, or longer. In some embodiments, the treatment reduces recurrence of breast cancer (e.g., an early breast cancer such as a HR+ / HER2- early breast cancer). The treatment may reduce recurrence for at least about 3 months, at least about 6 months, at least about 12 months, at least about 18 months, at least about 24 months, at least about 30 months, at least about 36 months, at least about 42 months, at least about 48 months, at least about 54 months, at least about 60 months, at least about 66 months, at least about 72 months, at least about 78 months, at least about 84 months, at least about 90 months, at least about 96 months, at least about 102 months, at least about 108 months, at least about 114 months, at least about 120 months, or longer. Recurrence of breast cancer may be an ipsilateral breast tumor recurrence (IBTR), defined herein as the reappearance of breast tumor in the same (i.e., ipsilateral) breast or chest wall. Recurrence of breast cancer may be a contralateral breast cancer, defined herein as a primary breast cancer that occurs in the opposite (i.e., contralateral) breast at least three months after the first breast cancer. Thus, in some embodiments, the method described herein comprises maintaining in remission an adult patient who had previously been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, in combination with an aromatase inhibitor. In some embodiments, the treatment described herein is an adjuvant therapy (also called an adjuvant treatment) to a prior treatment. The adjuvant therapy may follow any prior treatment, for example, the prior treatments described herein. The adjuvant therapy may follow more than one prior treatment. For example, one prior treatment may have been a neoadjuvant treatment preceding a primary treatment (e.g., first-line treatment) such as surgery with subsequent PAT059494-WO-PCT chemotherapy, radiation therapy and / or endocrine therapy, after which the treatment described herein is administered as an adjuvant therapy. Accordingly, in some embodiments, the method described herein comprises preventing breast cancer recurrence in an adult patient, comprising providing adjuvant treatment to a patient who has received a prior treatment for HR+ / HER2- stage II or III early breast cancer, wherein the adjuvant treatment comprises administering to the patient 400 mg ribociclib or a pharmaceutically acceptable salt thereof on days 1 to 21 of a 28-day cycle for at least 36 months, in combination with an aromatase inhibitor as defined herein on every day of the 28- day cycle. Accordingly, in some embodiments, the method described herein comprises maintaining remission an adult patient who had previously been diagnosed with an HR+ / HER2- stage II or stage III early breast cancer, comprising providing adjuvant treatment to a patient who has received a prior treatment for HR+ / HER2- stage II or III early breast cancer, wherein the adjuvant treatment comprises administering to the patient 400 mg ribociclib or a pharmaceutically acceptable salt thereof on days 1 to 21 of a 28-day cycle for at least 36 months, in combination with an aromatase inhibitor as defined herein administered on every day of the 28-day cycle. In some embodiments, the adjuvant treatment does not include administration of a 600 mg / day dose of ribocicilib. A further aspect of the present disclosure relates to a method of treating an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant therapy comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle, wherein the method results in an improvement in the patient in one or more of their overall survival (OS), distant disease-free survival (DDFS), or recurrence free survival (RFS). In some embodiments, the early breast cancer may no longer be in stage II or stage III when the treatment described herein begins. For example, the patient may have received at least one prior treatment, for which the treatment described herein is an adjuvant treatment. Another aspect of the present disclosure relates to a method for improving one or more of overall survival (OS), distant disease-free survival (DDFS), or recurrence free survival (RFS) in a patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, (ii) an aromatase inhibitor administered on every day of the 28-day cycle. PAT059494-WO-PCT A further aspect of the present disclosure relates to ribociclib for use in a method of improving one or more of overall survival (OS), distant disease-free survival (DDFS), or recurrence free survival (RFS) in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. The methods described herein may prevent local and / or regional invasive recurrence of early breast cancer. Accordingly, an aspect of the present disclosure relates to a method for reducing the risk of local or regional invasive recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. An aspect of the present disclosure relates to ribociclib for use in a method of reducing the risk of local or regional invasive recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle The method described herein may prevent recurrence of cancer in tissues outside of the breast, such as bone, liver, and lung or pleura. Thus, a further aspect of the present disclosure relates to a method for reducing the risk of invasive recurrence of early breast cancer in one or more of the bone, liver, and lung or pleura of an adult patient, who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. A further aspect of the present disclosure relates to ribociclib for use in a method of reducing the risk of invasive recurrence of early breast cancer in one or more of the bone, liver, and lung or pleura of an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days PAT059494-WO-PCT 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. Treatment may be administered irrespective of the nodal status of the breast cancer. Another aspect of the present disclosure relates to a method for reducing the risk of recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle and (ii) an aromatase inhibitor administered on every day of the 28-day cycle, wherein the treatment is administered irrespective of the nodal status of the breast cancer. An aspect of the present disclosure relates to ribociclib for use in a method of reducing the risk of recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle, wherein the treatment is administered irrespective of the nodal status of the breast cancer. For example, the breast cancer may have a nodal status of N0, N1, N2 or N3. The breast cancer may have a nodal status of N0. In some embodiments, the early breast cancer is stage II, for example stage IIA. In some embodiments, the early breast cancer is stage III, for example stage IIIB or IIIC. In certain embodiments, the breast cancer is of the ductal subtype. In some embodiments, the patient is Asian. An adjuvant treatment may be needed after a patient has received at least one prior treatment for breast cancer. In some embodiments, the method described herein is an adjuvant treatment because the patient has received at least one prior treatment for breast cancer selected from the group consisting of surgery, chemotherapy, and radiation therapy. In some embodiments, the patient has not had a mastectomy. In some embodiments, the dose of ribociclib is 400 mg / day. The ribociclib may be administered in the form of a salt, preferably as ribociclib succinate. In some embodiments, the aromatase inhibitor is letrozole or anastrozole. For example, the aromatase inhibitor may be letrozole, preferably administered in a dose of 2.5 mg / day. The aromatase inhibitor may be anastrozole, preferably administered in a dose of 1 mg / day. PAT059494-WO-PCT In some embodiments, the dose of ribociclib is 400 mg / day, the ribociclib is administered in the form of ribociclib succinate, and the aromatase inhibitor is letrozole or anastrozole, preferably 2.5 mg / day of letrozole or 1 mg / day anastrozole. In some embodiments, the improvement in OS, DDFS and / or RFS, or the reduction in the risk of recurrence of the breast cancer, are achieved in the patient for at least 36 months. In some embodiments, the patient has not previously received a CDK4 / 6 inhibitor. In some embodiments, the patient has not received tamoxifen, raloxifene, or aromatase inhibitors for reduction in risk (“chemoprevention”) of breast cancer and / or treatment for osteoporosis within the last 2 years prior to undergoing the present methods. In some embodiments, the patient has not received treatment with anthracyclines at cumulative doses of 450 mg / m² or more for doxorubicin, or 900 mg / m² or more for epirubicin prior to undergoing the present methods. In some embodiments, the patient does not have a known hypersensitivity to any of the excipients of ribociclib and / or ET (e.g., the patient does not have rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, or a soy allergy). In some embodiments, the patient does not receive other anti-neoplastic therapy, except for adjuvant ET as described herein. In some embodiments, the patient has not undergone major surgery, chemotherapy, or radiotherapy within 14 days of undergoing the present methods. In some embodiments, the patient has not recovered from clinical and laboratory acute toxicities related to prior anti-cancer therapies to a NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.03 Grade ≤ 1 at day of randomization. Exceptions are patients with any grade of alopecia, amenorrhea, grade 2 neuropathy, or other toxicities not considered a safety risk for the patient. In some embodiments, the patient does not have a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before randomization. Patients may have been adequately treated for basal or squamous cell skin carcinoma or had a curatively resected cervical cancer in situ. In some embodiments, the patient does not have a known history of human immunodeficiency virus (HIV) infection. In some embodiments, the patient does not have a known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (testing is not mandatory, unless required by local regulation). PAT059494-WO-PCT In some embodiments, the patient does not have clinically significant, uncontrolled heart disease and / or cardiac repolarization abnormality, including any of the following: • History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft within 6 months prior to undergoing the present methods. • Documented cardiomyopathy. • Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO). • Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: • Risk factors for Torsades de Pointes (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant / symptomatic bradycardia. • Concomitant medication(s) with a known risk to prolong the QT interval and / or known to cause TdP that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to undergoing the present methods). • Inability to determine the QTcF interval. • Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, and / or high-grade Atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third degree AV block). • Uncontrolled arterial hypertension with systolic blood pressure > 160 mmHg. In some embodiments, the patient has not received any of the following substances within 7 days before undergoing the present methods: • Concomitant medications, herbal supplements, and / or fruits (e.g. grapefruit, pummellos, starfruit, Seville oranges) and their juices that are known as strong inhibitors or inducers of CYP3A4 / 5. • Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4 / 5. In some embodiments, the patient does not to consume grapefruit (or grapefruit juice). In some embodiments, the patient does not consume pummellos, starfruit, and seville oranges (and their PAT059494-WO-PCT juices). In certain embodiments, the patient is not concomitantly using any of boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir, ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, and voriconazole. In some embodiments, the patient is not currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to undergoing the present methods, or has not fully recovered from side effects of such treatment. In some embodiments, a patient may use corticosteroids for the following: a short duration (<5 days) of systemic corticosteroids; any duration of topical applications (e.g. for rash), inhaled sprays (e.g. for obstructive airways diseases), eye drops or local injections (e.g. intra-articular). In some embodiments, the patient does not have an impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments (e.g. uncontrolled ulcerative diseases, uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, or small bowel resection). In some embodiments, the patient is not suffering from a concurrent severe and / or uncontrolled medical condition that may cause unacceptable safety risks, contraindicate patient treatment or compromise compliance with the methods (e.g. chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other significant liver disease, active untreated or uncontrolled fungal, bacterial or viral infections, active infection requiring systemic anti-bacterial therapy, etc.) or limit life expectancy to ≤5 years. In some embodiments, the patient has not been involved in treatment involving investigational drug(s) within 30 days prior to undergoing the present methods or within 5 half-lives of the investigational drug(s) (whichever is longer). IX. Additional criteria In some embodiments, the patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In some embodiments, the patient has bone marrow and organ function as defined by the following values: • Absolute neutrophil count (ANC) ≥ 1.5 × 109 / L. • Platelets ≥ 100 × 109 / L. • Hemoglobin ≥ 9.0 g / dL. PAT059494-WO-PCT • Estimated glomerular filtration rate (eGFR) ≥ 30 mL / min / 1.73m2according to the Modification of Diet in Renal Disease (MDRD) formula. • Alanine transaminase (ALT) < 2.5 × Upper Limit Normal (ULN). • Aspartate transaminase (AST) < 2.5 × ULN. • Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN in patients with well documented Gilbert’s Syndrome. • International normalized ratio (INR) ≤ 1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to randomization). • Laboratory values within normal limits or corrected to within normal limits with supplements (the local laboratory value should be documented within normal limits after the correction) for the following: • Potassium • Magnesium • Total Calcium (corrected for serum albumin) In some embodiments, the patient has standard 12-lead ECG values of QTcF interval (QT interval using Fridericia’s correction) at screening < 450 msec, and a resting heart rate 50-90 beats per minute (determined from the ECG). X. Region and race / ethnicity In some embodiments, the patient is located in North America. The patient may be located in Europe, for example, Western Europe. The patient may be located in Oceania, for example, in Australia. In some embodiments, the patient is located in Asia. In some embodiments, the patient is located in Africa. In some embodiments, the patient is located in Latin America. In some embodiments, the patient may be American Indian. In some embodiments, the patient may be Alaska Native. In some embodiments, the patient may be Asian. In some embodiments, the patient may be Black or African American. In some embodiments, the patient may be Native Hawaiian or Other Pacific Islander. In some embodiments, the patient may be White. In some embodiments, the patient may be a mixed race. In some embodiments, the patient may be non- Asian. In some embodiments, the patient may be Hispanic or Latino. In some embodiments, the patient is not Hispanic or Latino. PAT059494-WO-PCT E. Efficacy readouts An present disclosure relates to a method of treatment for early breast cancer in an adult patient in need thereof, comprising administering to the patient a treatment comprising a cyclin-dependent kinase (CDK) inhibitor in combination with endocrine therapy (ET), wherein the treatment is characterized by an improvement in the patient’s condition, as compared to a patient not receiving the treatment or as compared to the patient prior to treatment. In some embodiments, treatment regimens, e.g., the selection of a dose of ribociclib and / or aromatase inhibitor is chosen to achieve certain improvement in the patient’s condition, as compared to a patient not receiving the treatment or as compared to the patient prior to treatment. In some embodiments, a patient not receiving the treatment described herein may comprise a patient who does not receive ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate). In some embodiments, the patient not receiving the treatment described herein may comprise a patient who does not receive a combination of ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) and endocrine therapy. For example, the patient may receive only endocrine therapy alone, without ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate). The patient may receive letrozole alone without ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate). The patient may receive anastrozole alone without ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate). In some embodiments, the patient not receiving the treatment described herein may receive another cancer treatment, wherein the other cancer treatment is not a combination of ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) and endocrine therapy. In some embodiments, the patient not receiving the treatment described herein may be a patient who does not receive any cancer treatment. The improvement in the patient’s condition may relate to a reduction in signs and / or symptoms of breast cancer. For example, the improvement may comprise a reduction in breast cancer progression and / or breast cancer recurrence. The improvement may comprise prevention of breast cancer progression, early breast cancer recurrence, and / or death from the breast cancer. The improvement may comprise a reduction in the risk for cancer progression, cancer recurrence, and / or risk of (or avoidance of) death from the cancer. In some embodiments, the improvement in the patient’s condition is the maintenance of the existing signs and / or symptoms of breast cancer. For example, after treatment, the breast cancer may have about the same characteristics as before treatment, but no further progression of the breast cancer or worsening of the characteristics. PAT059494-WO-PCT In some embodiments, the improvement in the patient’s condition is an improvement as compared to a patient not receiving the treatment. In some embodiments, the patient not receiving the treatment receives another treatment for early breast cancer. In some embodiments, the patient not receiving the treatment receives only endocrine therapy alone. In some embodiments, the improvement in the patient’s condition may comprise one or more of a reduction in tumor size, prevention of spread of the tumor, prevention or reduction in recurrence of breast cancer, prevention of a second primary malignancy, and increased survival. For the example, the improvement in the patient’s condition may comprises an absence of (or a reduction in) locoregional relapse, distant relapse, ipsilateral and contralateral invasive breast cancers and second primary non-breast invasive cancer. In some embodiments, the improvement in the patient’s condition relates to measurements such as disease-free survival (DFS), invasive disease-free survival (iDFS), overall survival (OS), distant disease-free survival (DDFS), recurrence-free survival (RFS), and loco-regional recurrence-free survival (LLRFS). Disease-free survival (DFS) may relate to the length of time that a patient survives without local recurrence, contralateral recurrence, distant disease, secondary cancers, or new primary cancers. DFS may be defined as the time from a first date (e.g., a date when the treatment for cancer begins or, alternatively, a date when the treatment for cancer ends) to a date that the patient shows recurrence of a cancer or death. Invasive disease-free survival (iDFS) may be defined as DFS, but excluding ductal carcinoma in situ as a recurrence event. Overall survival (OS) may relate to the length of time that a patient survives, which can include death from any cause, regardless of whether the breast cancer has recurred or spread. OS may be defined as the time from a first date (e.g., a date when the treatment for cancer begins or, alternatively, a date when the treatment for cancer ends) to a date of death due to any cause. Distant disease-free survival (DDFS) may relate to the length of time during which a patient remains free of the cancer recurring at a distant site, e.g., not in the original breast. DDFS may be defined as the time from a first date (e.g., a date when the treatment for cancer begins or, alternatively, a date when the treatment for cancer ends) to a date of first event of distant recurrence, death (any cause), or second primary non-breast invasive cancer (excluding basal and squamous cell carcinomas of the skin). Recurrence free survival (RFS) may relate to any recurrence (local, regional, or distant) of the original breast cancer, but does not include new cancer(s). RFS may be defined as the time PAT059494-WO-PCT from a first date (e.g., a date when the treatment for cancer begins or, alternatively, a date when the treatment for cancer ends) to a date of first event of local invasive breast recurrence, regional invasive recurrence, distant recurrence, or death (any cause). Loco-regional recurrence-free survival (LRRFS) may be defined as the time from a first date (e.g., a date when the treatment for cancer begins or, alternatively, a date when the treatment for cancer ends) to a date of first event of local (ipsilateral) invasive breast recurrence, regional invasive recurrence, or death due to any cause. Accordingly, in some embodiments, the present methods improve one or more of DFS, iDFS, OS, DDFS, RFS, and LLRFS in a patient who receives the treatment as compared to a patient who does not receive the treatment. For example, the improvement in the patient’s condition may be a prolongation of the time period between a first date (e.g., a date when the treatment for cancer begins or, alternatively, a date when the treatment for cancer ends) and a date of occurrence of an event as defined in any of DFS, iDFS, OS, DDFS, RFS, and LLRFS. In some embodiments, the improvement in the patient’s condition is a decrease in the incidence (or decrease in the time until occurrence) of one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, distant recurrence (e.g., presence of metastasis), death from breast cancer, death from a non-breast cancer cause, death from an unknown cause, presence of invasive contralateral breast cancer, and presence of a second primary invasive cancer. For example, the treatment may decrease the incidence (or the time until occurrence) of death from breast cancer, death from a non-breast cancer cause, and death from an unknown cause. In some embodiments, the improvement in the patient’s condition is a decrease in the incidence (or decrease in the time until occurrence) of distant recurrence (e.g., presence of metastasis), death from breast cancer, death from a non-breast cancer cause, death from an unknown cause, and presence of a second primary invasive cancer. In some embodiments, the improvement in the patient’s condition is a decrease in the incidence (or decrease in the time until occurrence) of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, distant recurrence (e.g., presence of metastasis), death from breast cancer, death from a non-breast cancer cause, and death from an unknown cause. In some embodiments, the improvement in the patient’s condition is a decrease in the incidence (or decrease in the time until occurrence) of one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, death from breast cancer, death from a non-breast cancer cause, and death from an unknown cause. PAT059494-WO-PCT Where the improvement in the patient’s condition is a reduction in the risk of invasive disease or other events related to cancer, the risk may be determined using different measures. In some embodiments, the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than about 1 when the risk is calculated relative to patients not receiving the treatment. For example, the hazard ratio may be less than about 0.9, about 0.8, about 0.7, about 0.6, about 0.5, about 0.4, about 0.3, about 0.2, or about 0.1)For example, the hazard ratio for iDFS may be calculated using model such as an unstratified and covariate unadjusted Cox model or a stratified and covariate adjusted Cox model, as described in Appendix A. In some embodiments, the hazard ratio may be less than or equal to about 0.78. The hazard ratio may be less than or equal to about 0.72. In some embodiments, the patient has HR+ / HER2- stage III early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to about 0.74 when the risk is calculated relative to patients not receiving the treatment. The hazard ratio may be less than or equal to about 0.76. In some embodiments, the treatment yields at least a 25% reduction in the risk of invasive disease corresponding to a hazard ratio of 0.75 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the treatment reduces the risk of invasive disease to a similar level for patient subgroups comprising patients with stage II early breast cancer, stage III early breast cancer, patients who are premenopausal women or men, and patients who are postmenopausal women. In some embodiments, treatment as disclosed herein may achieve the following hazard ratios for particular patients with HR+ / HER2- early breast cancer. In some embodiments, the patient is a woman and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.76 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is a pre-menopausal woman or a man and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.72 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is a post-menopausal woman and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.78 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient received a prior neo- / adjuvant chemotherapy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.73 when the risk is calculated relative to patients not receiving the treatment. PAT059494-WO-PCT In some embodiments, the patient is located in North America, Western Europe or Oceania, and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.76 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is not located in North America, Western Europe or Oceania, and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.76 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has stage II cancer and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.76 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has stage III cancer and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.74 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has stage IIA cancer and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.5 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has stage IIB cancer and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.93 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has stage IIIA cancer and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.79 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has stage IIIB cancer and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.68 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has stage IIIC cancer and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.69 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient received prior adjuvant chemotherapy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.67 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient did not receive prior adjuvant chemotherapy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.81 when the risk is calculated relative to patients not receiving the treatment. PAT059494-WO-PCT In some embodiments, the patient received prior neoadjuvant chemotherapy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.79 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient did not receive prior neoadjuvant chemotherapy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.72 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient received prior radiation therapy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.74 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient did not receive prior radiation therapy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.98 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient received prior endocrine therapy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.76 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient did not receive endocrine therapy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.77 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient had a prior mastectomy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.85 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient did not have a prior mastectomy and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.55 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is Asian and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.52 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is not Asian and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.81 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is located in Europe and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.88 when the risk is calculated relative to patients not receiving the treatment. PAT059494-WO-PCT In some embodiments, the patient is located in North America or Australia and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.70 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is located in Asia and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.34 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is located in Latin America and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.69 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is less than 45 years old and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.68 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is 45 to 54 years old and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.75 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is 55 to 64 and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.84 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is 65 years old or older and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.72 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient receives letrozole and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.79 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient receives anastrozole and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.70 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has ER+ / PR+ cancer and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.73 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has ER+ / PR- cancer and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.91 when the risk is calculated relative to patients not receiving the treatment. PAT059494-WO-PCT In some embodiments, the patient has a tumor with nodal status 0 and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.63 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a tumor with nodal status N1-N3 and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.77 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a tumor of category T1-T3 and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.74 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a tumor of a category greater than T3 (e.g., T4) and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.83 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a tumor with a histological grade 1 and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.78 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a tumor with a histological grade 1 and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.78 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a tumor with a histological grade 2 and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.75 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a tumor with a histological grade 3 and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.78 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a tumor with Ki67 status that is 20% or lower and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.80 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a tumor with Ki67 status that is greater than 20% and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.75 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a tumor of a ductal subtype and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.68 when the risk is calculated relative to patients not receiving the treatment. PAT059494-WO-PCT In some embodiments, the patient has a tumor that is not a ductal subtype or a lobular subtype and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.89 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a BMI of 25 or greater and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.85 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient has a BMI of less than 25 and the treatment may reduce the risk of invasive disease corresponding to a hazard ratio of less than about 0.64 when the risk is calculated relative to patients not receiving the treatment. For overall survival, the treatment may yield no deterioration in overall survival corresponding to a hazard ratio of 0.76 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the treatment does not cause or worsen events such as pneumonia, pulmonary embolism, dyspnoea, increased alanine aminotransferase, increased aspartate aminotransferase, arthralgia, fatigue, neutropenia, decreased neutrophil count, and / or nausea. In some embodiments, the treatment does not cause or worsen conditions related to hepatobiliary toxicity, for example, as measured by increases in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, blood alkaline phosphatase, and / or blood bilirubin. In some embodiments, the treatment does not cause or worsen conditions related to myelosuppression (e.g., anemia and / or leukopenia). For example, the treatment does not cause of worsen leukopenia, or lead to decreased white blood cell count, lymphopenia, or decreased lymphocyte count. In some embodiments, the treatment does not cause or worsen conditions related to myelosuppression (e.g., neutropenia, decreased neutrophil count, thrombocytopenia, decreased platelet count). In some embodiments, the treatment does not prolong the QT interval in an electrocardiogram. In some embodiments, the treatment does not cause or worsen conditions related to renal toxicity (e.g., increased blood creatinine, decreased glomerular filtration rate, increased blood urea). In some embodiments, the treatment does not cause or worsen conditions related to reproductive toxicity, such as mastitis. PAT059494-WO-PCT F. A method for treatment of HR+ / HER2- early breast cancer One aspect of the present disclosure relates a method of treatment for HR+ / HER2- stage II or III early breast cancer in an adult patient in need thereof, comprising administering to the patient a treatment comprising a dose of ribociclib (or a pharmaceutically acceptable salt thereof, such as ribociclib succinate) ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle in combination with an endocrine therapy (such as an aromatase inhibitor, preferably letrozole or anastrozole) administered on every day (e.g., days 1-28) of the 28-day cycle. A further aspect of the present disclosure relates to a method of preventing or reducing signs or symptoms of early stage breast cancer, comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle in combination with an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle. Another aspect of the present disclosure relates to a method of maintaining in remission an adult patient who had previously been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient a treatment comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle in combination with an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle. Still another aspect of the present disclosure relates to a method of preventing breast cancer recurrence in an adult patient, comprising providing adjuvant treatment to a patient who has received a prior treatment for HR+ / HER2- stage II or III early breast cancer, wherein the adjuvant treatment comprises administering to the patient 400 mg ribociclib or a pharmaceutically acceptable salt thereof on days 1 to 21 of a 28-day cycle for at least 36 months, in combination with an aromatase inhibitor as defined in any one of embodiments 23 to 28 administered on every day of the 28-day cycle. In some embodiments, the treatment comprises comprising administering to the patient a treatment comprising a dose of about 400 mg / day (or a dose of about 200 mg / day) ribociclib or a pharmaceutically acceptable salt thereof, such as ribociclib succinate, on days 1 to 21 of a 28- day cycle for 36 months, in combination with an endocrine therapy comprising a dose of letrozole ranging from about 1 mg / day to about 4 mg / day or a dose of anastrozole ranging from about 0.5 mg / day to about 1.5 mg / day administered on every day (e.g., days 1-28) of the 28-day cycle. PAT059494-WO-PCT In some embodiments, the treatment comprises administering to the patient a treatment comprising a dose of about 400 mg / day (or a dose of about 200 mg / day) ribociclib or a pharmaceutically acceptable salt thereof, such as ribociclib succinate, on days 1 to 21 of a 28- day cycle for 36 months, in combination with an endocrine therapy, wherein the endocrine therapy comprises a dose of letrozole of about 2.5 mg / day or a dose of anastrozole of about 1 mg / day administered on days 1-28 of the 28-day cycle. In some embodiments, the treatment reduces one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, distant recurrence (e.g., presence of metastasis), death from breast cancer, death from a non-breast cancer cause, death from an unknown cause, presence of invasive contralateral breast cancer, and presence of a second primary invasive cancer. In some embodiments, the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than about 1 when the risk is calculated relative to patients not receiving the treatment. For example, the hazard ratio for iDFS may be calculated using model such as an unstratified and covariate unadjusted Cox model or a stratified and covariate adjusted Cox model, as described in Appendix A. In some embodiments, the hazard ratio may be less than or equal to about 0.78. The hazard ratio may be less than or equal to about 0.72. In some embodiments, the patient has HR+ / HER2- stage III early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to about 0.74 when the risk is calculated relative to patients not receiving the treatment. The hazard ratio may be less than or equal to about 0.76. In some embodiments, the treatment yields at least a 25% reduction in the risk of invasive disease corresponding to a hazard ratio of 0.75 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the treatment reduces the risk of invasive disease to a similar level for patient subgroups comprising patients with stage II early breast cancer, stage III early breast cancer, patients who are premenopausal women or men, and patients who are postmenopausal women. For overall survival, the treatment may yield no deterioration in overall survival corresponding to a hazard ratio of 0.76 when the risk is calculated relative to patients not receiving the treatment. In some embodiments, the patient is a postmenopausal woman. In some embodiments, the patient is a premenopausal woman or a man. In some embodiments, the early breast cancer comprises a tumor of stage II. In some embodiments, the tumor may have an anatomic stage IIA. In some embodiments, the tumor PAT059494-WO-PCT may have an anatomic stage IIB. In some embodiments, the early breast cancer comprises a tumor of stage III. In some embodiments, the tumor may have an anatomic stage IIIA. In some embodiments, the tumor may have an anatomic stage IIIB. In some embodiments, the tumor may have an anatomic stage IIIC. In some embodiments, the patient has received prior neo-adjuvant chemotherapy. In some embodiments, the patient has received prior adjuvant chemotherapy. In some embodiments, the patient has received prior radiation therapy. In some embodiments, the patient has undergone a mastectomy. In some embodiments, the patient has not undergone a mastectomy. In some embodiments, the patient is located in North America. In some embodiments, the patient is located in Europe, for example, in Western Europe. In some embodiments, the patient is located in Oceania, for example, in Australia. In some embodiments, the patient is located in Latin America. In some embodiments, the patient is located in Asia. In some embodiments, the patient is Asian. In some embodiments, the patient is non-Asian. In some embodiments, the patient may be American Indian. In some embodiments, the patient may be Alaska Native. In some embodiments, the patient may be Black or African American. In some embodiments, the patient may be Native Hawaiian or Other Pacific Islander. In some embodiments, the patient may be White. In some embodiments, the patient may be a mixed race. In some embodiments, the patient may be non-Asian. In some embodiments, the patient may be Hispanic or Latino. In some embodiments, the patient is not Hispanic or Latino. In some embodiments, the patient is 18 years or older. The patient may be 18-44 years old. The patient may be 45-54 years old. The patient may be 55 to 64 years old. The patient may be 65 years or older. In some embodiments, the endocrine therapy is a non-steroidal aromatase inhibitor (NSAI). In some embodiments, the NSAI may be letrozole. In some embodiments, the NSAI may be anastrozole. In some embodiments, the early breast cancer is selected from a ER+ / PR+, a ER- / PR+, and a ER+ / PR- breast cancer. In some embodiments, the treatment is administered irrespective of the nodal status of the breast cancer. In some embodiments, the early breast cancer has a nodal status of N0, N1, N2, or N3. PAT059494-WO-PCT In some embodiments, the early breast cancer comprises a tumor of category T0, category T1, T2, T3, or T3. In some embodiments, the early breast cancer has a histological grade at time of surgery of G1, G2, or G3. In some embodiments, the early breast cancer has a Ki67 status (e.g., from an archival tumor) of 20 or less than 20. Alternatively, the early breast cancer may have a Ki67 status of greater than 20. In some embodiments, the early breast cancer has a ductal histological subtype or a lobular histological subtype. An aspect of the present disclosure relates to a method of preventing recurrence of breast cancer in an adult patient who has received a prior treatment for HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, and (ii) a dose of an aromatase inhibitor, preferably letrozole or anastrozole. A further aspect of the present disclosure relates to a method of treating an adult patient in remission from HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, and (ii) a dose of an aromatase inhibitor, preferably letrozole or anastrozole. Another aspect of the present disclosure relates to a method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient in need thereof, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle and (ii) an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle. One aspect of the present disclosure relates to a method of treating breast cancer recurrence in an adult patient who has received at least one prior treatment for HR+ / HER2- stage II or III early breast cancer and who has no detectable signs or symptoms of breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1 to 21 of a 28-day cycle, and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle. An additional aspect of the present disclosure relates to a method of treating an adult patient who is in remission from HR+ / HER2- stage II or stage III early breast cancer and in need of adjuvant treatment, comprising administering to the patient an adjuvant treatment comprising (i) PAT059494-WO-PCT a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1- 21 of a 28-day cycle and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle. In some embodiments, the patient has a BMI of 25 or greater. In some embodiments, the patient has a BMI of less than 25. A further aspect of the present disclosure relates to a method of preventing or reducing signs or symptoms of early stage breast cancer, comprising administering to the patient a treatment comprising ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof in combination with an aromatase inhibitor, preferably letrozole or anastrozole. In some embodiments, the ribociclib is a freebase form thereof or a pharmaceutically acceptable salt thereof, and is administered to the patient in a dose ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle. In some embodiments, the aromatase inhibitor is administered on every day of the 28-day cycle. G. A patient in remission One aspect of the present disclosure relates a method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient in remission, comprising administering to the adult patient ribociclib in combination with an aromatase inhibitor whereby the administration maintains the adult patient in remission for at least about 3 months. A further aspect relates to a method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient, comprising providing adjuvant treatment by administering ribociclib in combination with aromatase inhibitor, wherein the patient at start of the adjuvant treatment is in complete remission, and the administration of ribociclib in combination with an aromatase inhibitor maintains the adult patient in complete remission for at least about 3 months. The administration of ribociclib in combination with an aromatase inhibitor may maintain the adult patient in remission (e.g., complete remission) for a period of time that is at least about 3 months. In some embodiments, the administration maintains the adult patient in remission for at least about 6 months. In some embodiments, the administration maintains the adult patient in remission for at least about 9 months. In some embodiments, the administration maintains the adult patient in remission for at least about 12 months. In some embodiments, the administration maintains the adult patient in remission for at least about 15 months. In some embodiments, the administration maintains the adult patient in remission for at least about 18 months. In some embodiments, the administration maintains the adult patient in remission for at least about 21 months. In some embodiments, the administration maintains the adult patient in PAT059494-WO-PCT remission for at least about 24 months. In some embodiments, the administration maintains the adult patient in remission for at least about 27 months. In some embodiments, the administration maintains the adult patient in remission for at least about 30 months. In some embodiments, the administration maintains the adult patient in remission for at least about 33 months. In some embodiments, the administration maintains the adult patient in remission for at least about 36 months. In certain embodiments, ribociclib and an aromatase inhibitor are administered for a treatment duration, and the administration maintains the adult patient in remission for at least the treatment duration. For the methods described herein, the dose and treatment schedule for the combination of ribociclib and an aromatase inhibitor may follow the exemplary embodiments as follows. In some embodiments, a dose of 400 mg ribociclib is orally administered once daily on days 1-21 of a 28-day cycle and aromatase inhibitor is administered once daily on each day of the 28-day cycle. A dose of 400 mg ribociclib is orally administered once daily on days 1-21 of a 28-day cycle for a treatment duration of up to three years and aromatase inhibitor is administered once daily on each day of the 28-day cycle for the up to three years. For example, a dose of 400 mg ribociclib may be orally administered once daily on days 1-21 of a 28-day cycle for a treatment duration of up to five years and aromatase inhibitor is administered once daily on each day of the 28-day cycle for the up to five years. In some embodiments, a pharmaceutically acceptable salt of ribociclib is orally administered in an amount corresponding to 400 mg ribociclib. The pharmaceutically acceptable salt may be ribociclib succinate. In some embodiments, the adult patient was never treated with a 600 mg dose of ribociclib. In some embodiments, the adult patient has never been diagnosed with HR+ / HER2- advanced or metastatic breast cancer. Ribociclib and aromatase inhibitor may be administered as adjuvant therapy. In some embodiments, the ribociclib is not administered at a dose of 600 mg / day. The dose of ribociclib may be administered in tablet form. For example, two tablets may be orally administered to the adult patient once daily on days 1-21 of a 28-day cycle repeating for a treatment duration, and each tablet contains an amount of a pharmaceutically acceptable ribociclib salt corresponding to 200 mg ribociclib. In some embodiments, the ribociclib salt is PAT059494-WO-PCT ribociclib succinate. In some embodiments, the aromatase inhibitor is letrozole. In some embodiments, the aromatase inhibitor is anastrazole. In some embodiments, the aromatase inhibitor is letrozole, and the letrozole is administered in a dose ranging from 1 mg to 4 mg once daily. For example, the aromatase inhibitor may be letrozole, and the letrozole may be administered in a dose of 2.5 mg once daily. In some embodiments, the aromatase inhibitor is anastrozole, and the anastrozole is administered in a dose ranging from 0.5 mg once daily to 1.5 mg once daily. For example, anastrozole may be administered in a dose of 1 mg once daily. The method of any one of embodiments 117 to 148, wherein the patient is a postmenopausal woman. In some embodiments, the patient is a premenopausal woman or a man. The patient may be a premenopausal woman or a man. Some embodiments, for example, where the patient is a premenopausal woman or man, further comprise administering to the adult patient a gonadotropin-releasing hormone agonist. In some embodiments, the gonadotropin-releasing hormone agonist is goserelin. In some embodiments, the goserelin is administered in a dose ranging from 2 mg to 5 mg. For example, the dose of goserelin may be 3.6 mg. In some embodiments, the goserelin is administered subcutaneously. In some embodiments, the goserelin is administered once every 4 weeks. In some embodiments, the breast cancer has a histological subtype that is ductal or a histological subtype that is lobular. In some embodiments, the breast cancer is a stage IIA cancer or a stage IIB cancer. For example, the breast cancer may be a stage IIA cancer. The breast cancer may be a stage IIB cancer. In some embodiments, the breast cancer is a stage IIIA cancer, a stage IIIB cancer, or a stage IIIC cancer. For example, the breast cancer may be a stage IIIA cancer. The breast cancer may be a stage IIIB cancer. The breast cancer may be a stage IIIC cancer. In some embodiments, the treatment is administered irrespective of the nodal status of the breast cancer. In some embodiments, treatment with ribociclib and aromatase inhibitor is not adjusted on the basis of the nodal status of the early breast cancer. In some embodiments, the breast cancer has a nodal status selected from N0, N1, N2, and N3. For example, the breast cancer may have a nodal status of N0. The breast cancer may have a nodal status of N1-N3. The breast cancer may have a nodal status of N1. The breast cancer may have a nodal status of N2. The breast cancer may have a nodal status of N3. PAT059494-WO-PCT In some embodiments, the breast cancer comprises one or more cells having a histological grade selected from G1, G2, or G3. For example, the breast cancer may comprise one or more cells having the histological grade G1. The breast cancer may comprise one or more cells having the histological grade G2. The breast cancer may comprise one or more cells having the histological grade G3. In some embodiments, the breast cancer comprises a tumor of category T0, T1, T2, T3, or T4. For example, the breast cancer may comprise a tumor of category T1, T2, or T3. The breast cancer may comprise a tumor of category T0. The breast cancer may comprise a tumor of category T1. The breast cancer may comprise a tumor of category T2. The breast cancer may comprise a tumor of category T3. The breast cancer may comprise a tumor of category T4. In some embodiments, the breast cancer has a Ki67 status of 20 or lower. In some embodiments, the breast cancer has a Ki67 status of greater than 20. In some embodiments, prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had surgery for the early breast cancer. In some embodiments, prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had (1) surgery for the early breast cancer, followed by (2) chemotherapy. In some embodiments, prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had (1) surgery for the early breast cancer, followed by (2) chemotherapy and / or endocrine therapy. In some embodiments, the endocrine therapy was therapy with a prior aromatase inhibitor. The prior aromatase inhibitor may have been letrozole or anastrozole. In some embodiments, immediately prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had surgery for the early breast cancer. In some embodiments, wherein the surgery comprised a complete surgical resection of the cancer. In some embodiments, the surgery was a mastectomy. In some embodiments, the patient received neoadjuvant therapy. For example, the neoadjuvant therapy may have been chemotherapy. In some embodiments, the adult patient is located in a geographic region selected from North America, Western Europe, or Oceania. In some embodiments, the patient is Asian. PAT059494-WO-PCT In some embodiments, the patient is 18 to 45 years of age. In some embodiments, the patient is 45 to 54 years of age. In some embodiments, the patient is 54 to 64 years of age. In some embodiments, the patient is greater than 64 years of age. In some embodiments, wherein the patient has a BMI of 25 or higher. In some embodiments, the patient has a BMI lower than 25. In some embodiments, the treatment improves a condition of the patient relative to a patient not receiving the treatment and / or relative to the condition in the patient prior to treatment. In some embodiments, the treatment reduces the risk of invasive disease. For example, The treatment may reduces the risk of invasive disease in the adult patient corresponding to a hazard ratio of less than 1 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. In some embodiments, the treatment reduces the risk of invasive disease in the adult patient corresponding to a hazard ratio of less than or equal to 0.78 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. In some embodiments, the adult patient is a premenopausal woman or a man and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.72 when the risk is calculated relative to other premenopausal women or men, respectively, having received the same treatment as the premenopausal woman or man, respectively, except that the other premenopausal women or men did not receive the ribociclib. In some embodiments, the adult patient was diagnosed with HR+ / HER2- stage III early breast cancer and the treatment reduces the risk of invasive disease in the adult patient corresponding to a hazard ratio of less than or equal to 0.74 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. In some embodiments, the adult patient was diagnosed with HR+ / HER2- stage II early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.76 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. In some embodiments, the adult patient was diagnosed with HR+ / HER2- stage III early breast cancer, and the treatment yields at least a 25% reduction in the risk of invasive disease corresponding to a hazard ratio of 0.75 when the risk is calculated relative to other patients having PAT059494-WO-PCT received the same treatment as the adult patient except that the other patients did not receive the ribociclib. In some embodiments, the treatment reduces the risk of invasive disease to a similar level for patient subgroups comprising patients with stage II early breast cancer, stage III early breast cancer, patients who are premenopausal women or men, and patients who are postmenopausal women. In some embodiments, the treatment yields no deterioration in overall survival corresponding to a hazard ratio of 0.76 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. In some embodiments, the treatment reduces and / or prevents one or more of recurrence of the cancer, spread of the cancer, development and / or growth of an additional cancer, and risk of death from the cancer. In some embodiments, the treatment reduces the recurrence of cancer, wherein the recurrence is one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, and distant recurrence. In some embodiments, the treatment reduces the spread of cancer, wherein the spread of cancer is an invasive contralateral breast cancer or an additional primary invasive cancer. A further aspect of the present disclosure relates to ribociclib or a pharmaceutically acceptable salt thereof and an aromatase inhibitor for use in a method of treatment for HR+ / HER2- stage II or III early breast cancer in an adult patient, wherein the method is any one of the methods described herein. Another aspect of the present disclosure relates to the use of ribociclib or a pharmaceutically acceptable salt thereof and an aromatase inhibitor in the manufacture of a medicament for treating HR+ / HER2- stage II or III early breast cancer in an adult patient, wherein the medicament is administered by any one of the methods described herein. Another aspect of the present disclosure relates to a kit for performing a method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient according to any one of the methods described herein. PAT059494-WO-PCT H. A kit for uses and methods One aspect of the present disclosure provides a kit for performing the methods disclosed herein, for example, a kit for performing a method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient. The kit may be promoted, distributed, or sold as a unit for performing the methods of the present invention. In some embodiments, the kit comprises a dose of ribiciclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, and a dose of an aromatase inhibitor such as letrozole or anastrozole. The kit may comprise guidance and / or instructions, e.g., a schedule for administration of the ribociclib and / or the aromatase inhibitor. In some embodiments, the kit comprises a dose of ribociclib ranging from about 150 mg / day to 450, and guidance and / or instructions to administer the ribociclib on days 1-21 of a 28-day cycle. The kit may further comprise a dose of an aromatase inhibitor such as letrozole or anastrozole, for example, a dose of about 2.5 mg / day letrozole or about 1 mg / day anastrozole, and may further comprise guidance and / or instructions to administer the aromatase inhibitor on every day of the 28-day cycle. In some embodiments, the kit comprises a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day and a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole. The kit may further comprise guidance and / or instructions to administer the dose of ribociclib succinate on days 1 to 21 of a 28-day cycle, and to administer the dose of letrozole or anastrozole administered on every day of the 28-day cycle. Exemplary kits may comprise more than 1 daily dose, for example, a kit may comprise 21 doses of the ribociclib, or freebase form thereof or a pharmaceutically acceptable salt thereof, and 28 doses of the aromatase inhibitor (e.g., letrozole or anastrozole), for administration over the whole 28-day cycle. Other exemplary kits may comprise doses of ribociclib, or freebase form thereof or a pharmaceutically acceptable salt thereof, and the aromatase inhibitor (letrozole or anastrozole) for multiple 28-day cycles. I. Exemplary embodiments The methods of treatment and medical uses of the present disclosure are provided in the following embodiments. 1. A method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient in need thereof, comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, PAT059494-WO-PCT ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle in combination with an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle. 2. A method of preventing or reducing signs or symptoms of early stage breast cancer, comprising administering to the patient a treatment comprising ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof in combination with an aromatase inhibitor, preferably letrozole or anastrozole. 3. The method of embodiment 2, wherein the the ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, is administered to the patient in a dose ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle. 4. The method of embodiment 2 or 3, wherein the aromatase inhibitor is administered on every day of the 28-day cycle. 5. A method of preventing or reducing signs or symptoms of early breast cancer, comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle in combination with an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle. 6. The method of any one of embodiments 1 to 5, wherein the patient is in remission from HR+ / HER2- stage II or stage III early breast cancer. 7. A method of maintaining remission in an adult patient who had previously been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, in combination with an aromatase inhibitor, preferably letrozole or anastrozole. 8. The method of embodiment 6 or embodiment 7, wherein the remission is complete remission. 9. The method of embodiment 6 or embodiment 7, wherein the remission is partial remission. 10. The method of any one of embodiments 1 to 9, wherein the treatment reduces recurrence of HR+ / HER2- stage II or stage III early breast cancer. PAT059494-WO-PCT 11. The method of embodiment 10, wherein the treatment prevents recurrence for at least 3 months. 12. The method of embodiment 11, wherein the treatment prevents recurrence for at least 6 months. 13. The method of embodiment 12, wherein the treatment prevents recurrence for at least 1 year. 14. The method of any one of embodiments 1 to 13, wherein the patient has no signs or symptoms of cancer prior to receiving the treatment. 15. The method of any one of embodiments 1 to 14, wherein the treatment prevents growth of HR+ / HER2- breast cancer cells. 16. The method of any one of embodiments 1 to 15, wherein the treatment is an adjuvant therapy. 17. The method of any one of embodiments 1 to 16, wherein the ribociclib is a pharmaceutically acceptable ribociclib salt. 18. The method of embodiment 17, wherein the ribociclib salt is ribociclib succinate. 19. The method of any one of embodiments 1 to 18, wherein the dose of ribociclib is 200 mg / day or 400 mg / day. 20. The method of any one of embodiments 1 to 18, wherein the ribociclib is not administered at a dose of 600 mg / day. 21. The method of any one of embodiments 1 to 19, wherein ribociclib is administered as ribociclib succinate, and the total dose of ribociclib is 200 mg / day. 22. The method of any one of embodiments 1 to 19, wherein ribociclib is administered as ribociclib succinate, and the total dose of ribociclib is 400 mg / day. 23. The method of any one of embodiments 1 to 19, wherein the ribociclib is administered at a dose of 400 mg / day for a period of time, after which a dose of 200 mg / day ribociclib is administered. 24. The method of any one of embodiments 1 to 23, wherein the dose of ribociclib is administered orally. PAT059494-WO-PCT 25. The method of any one of embodiments 1 to 24, wherein the dose of ribociclib is administered in tablet form. 26. The method of any one of embodiments 1 to 24, wherein the aromatase inhibitor is letrozole or anastrozole. 27. The method of any one of embodiments 1 to 26, wherein the aromatase inhibitor is administered orally. 28. The method of embodiment 26 or 27, wherein the letrozole is administered in a dose ranging from 1 mg / day to 4 mg / day. 29. The method of embodiment 28, wherein the letrozole is administered in a dose of 2.5 mg / day. 30. The method of embodiment 26 or 27, wherein the anastrozole is administered in a dose ranging from 0.5 mg / day to 1.5 mg / day. 31. The method of embodiment 30, wherein the anastrozole is administered in a dose of 1 mg / day. 32. The method of any one of embodiments 1 to 31, wherein the treatment comprises a gonadotropin-releasing hormone agonist. 33. The method of embodiment 32, wherein the gonadotropin-releasing hormone agonist is goserelin. 34. The method of embodiment 33, wherein the goserelin is administered in a dose ranging from 2 mg to 5 mg. 35. The method of embodiment 34, wherein the dose of goserelin is 3.6 mg. 36. The method of any one of embodiments 33 to 35, wherein the goserelin is administered subcutaneously. 37. The method of any one of embodiments 33 to 36, wherein the goserelin is administered once every 4 weeks. 38. The method of any one of embodiments 1 to 31, wherein the patient is a postmenopausal woman. PAT059494-WO-PCT 39. The method of any one of embodiments 1 to 37, wherein the patient is a premenopausal woman or a man. 40. The method of any one of embodiments 1 to 39, wherein the treatment is administered to the patient for at least 12 months. 41. The method of embodiment 40, wherein the treatment is administered to the patient for at least 24 months. 42. The method of embodiment 40 or embodiment 41, wherein the treatment is administered to the patient for at least 36 months. 43. The method of any one of embodiments 40 to 41, wherein the treatment is administered to the patient for at least 48 months. 44. The method of any one of embodiments 40 to 41, wherein the treatment is administered to the patient for at least 60 months. 45. The method of any one of embodiments 1 to 44, wherein the treatment continues until the patient has no detectable cancer. 46. The method of any one of embodiments 1 to 45, wherein the breast cancer is ER+ and PR+. 47. The method of any one of embodiments 1 to 45, wherein the breast cancer is ER- and PR+. 48. The method of any one of embodiments 1 to 45, wherein the breast cancer is ER+ and PR-. 49. The method of any one of embodiments 1 to 48, wherein the breast cancer has a histological subtype that is ductal or a histological subtype that is lobular. 50. The method of any one of embodiments 1 to 49, wherein the breast cancer is a stage IIA cancer or a stage IIB cancer. 51. The method of embodiment 50, wherein the breast cancer is a stage IIA cancer. 52. The method of embodiment 50, wherein the breast cancer is a stage IIB cancer. 53. The method of any one of embodiments 1 to 49, wherein the breast cancer is a stage IIIA cancer, a stage IIIB cancer, or a stage IIIC cancer. PAT059494-WO-PCT 54. The method of embodiment 53, wherein the breast cancer is a stage IIIA cancer. 55. The method of embodiment 53, wherein the breast cancer is a stage IIIB cancer. 56. The method of embodiment 53, wherein the breast cancer is a stage IIIC cancer. 57. The method of any one of embodiments 1 to 56, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 58. The method of any one of embodiments 1 to 57, wherein the breast cancer has a nodal status selected from N0, N1, N2, and N3. 59. The method of embodiment 57 or 58, wherein the breast cancer has a nodal status of N0. 60. The method of embodiment 57 or 58, wherein the breast cancer has a nodal status of N1 to N3. 61. The method of embodiment 57 or 58, wherein the breast cancer has a nodal status of N1. 62. The method of embodiment 57 or 58, wherein the breast cancer has a nodal status of N2. 63. The method of embodiment 57 or 58, wherein the breast cancer has a nodal status of N3. 64. The method of any one of embodiments 1 to 63, wherein the breast cancer comprises one or more cells having a histological grade selected from G1, G2, or G3. 65. The method of embodiment 64, wherein the breast cancer comprises one or more cells having the histological grade G1. 66. The method of embodiment 64, wherein the breast cancer comprises one or more cells having the histological grade G2. 67. The method of embodiment 64, wherein the breast cancer comprises one or more cells having the histological grade G3. 68. The method of any one of embodiments 1 to 67, wherein the breast cancer comprises a tumor of category T0, T1, T2, T3, or T4. PAT059494-WO-PCT 69. The method of embodiment 68, wherein the breast cancer comprises a tumor of category T1, T2, or T3. 70. The method of embodiment 68, wherein the breast cancer comprises a tumor of category T0. 71. The method of embodiment 68 or 69, wherein the breast cancer comprises a tumor of category T1. 72. The method of embodiment 68 or 69, wherein the breast cancer comprises a tumor of category T2. 73. The method of embodiment 68 or 69, wherein the breast cancer comprises a tumor of category T3. 74. The method of embodiment 68, wherein the breast cancer comprises a tumor of category T4. 75. The method of any one of embodiments 1 to 74, wherein the breast cancer has a Ki67 status of 20 or lower. 76. The method of any one of embodiments 1 to 74, wherein the breast cancer has a Ki67 status of greater than 20. 77. The method of any one of embodiments 1 to 76, wherein prior to the administration, the patient has received a loading dose of (i) ribociclib and / or (ii) an endocrine therapy. 78. The method of any one of embodiments 1 to 77, wherein the patient has received at least one prior treatment for cancer. 79. The method of embodiment 78, wherein the prior treatment is an adjuvant treatment after another prior treatment. 80. The method of embodiment 78 or 79, wherein the prior treatment is surgery. 81. The method of embodiment 80, wherein the surgery comprises a complete surgical resection of the cancer. 82. The method of embodiment 80 or 81, wherein the surgery is a mastectomy. 83. The method of embodiment 80 or 81, wherein the prior treatment is a chemotherapy. PAT059494-WO-PCT 84. The method of embodiment 83, wherein the prior treatment is an adjuvant chemotherapy. 85. The method of embodiment 83, wherein the prior treatment is a neoadjuvant chemotherapy. 86. The method of embodiment 78 or 79, wherein the prior treatment is an endocrine therapy. 87. The method of embodiment 78 or 79, wherein the prior treatment is radiation therapy. 88. The method of any one of embodiments 78 to 87, wherein the patient did not respond to the prior treatment. 89. The method of any one of embodiments 1 to 88, wherein the patient is located in a geographic region selected from North America, Western Europe, or Oceania. 90. The method of any one of embodiments 1 to 89, wherein the patient is Asian. 91. The method of any one of embodiments 1 to 90, wherein the patient is 18 to 45 years of age. 92. The method of any one of embodiments 1 to 90, wherein the patient is 45 to 54 years of age. 93. The method of any one of embodiments 1 to 90, wherein the patient is 54 to 64 years of age. 94. The method of any one of embodiments 1 to 90, wherein the patient is greater than 64 years of age. 95. The method of any one of embodiments 1 to 94, wherein the patient has a BMI of 25 or higher. 96. The method of any one of embodiments 1 to 94, wherein the patient has a BMI lower than 25. 97. The method of any one of embodiments 1 to 96, wherein the treatment improves a condition of the patient relative to a patient not receiving the treatment and / or relative to the condition in the patient prior to treatment. 98. The method of any one of embodiments 1 to 97, wherein the treatment reduces the risk of invasive disease. PAT059494-WO-PCT 99. The method of embodiment 98, wherein the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than 1 when the risk is calculated relative to patients not receiving the treatment. 100. The method of embodiment 99, wherein the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.78 when the risk is calculated relative to patients not receiving the treatment. 101. The method of any one of embodiments 1 to 37 and 39 to 100, wherein the patient is a premenopausal woman or a man and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.72 when the risk is calculated relative to patients receiving the treatment. 102. The method of any one of embodiments 98 to 100, wherein the patient has HR+ / HER2- stage III early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.74 when the risk is calculated relative to patients not receiving the treatment. 103. The method of any one of embodiments 98 to 100, wherein the patient has HR+ / HER2- stage II early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.76 when the risk is calculated relative to patients not receiving the treatment. 104. The method of any one of embodiments 98 to 100, wherein the patient has HR+ / HER2- stage III early breast cancer, and the treatment yields at least a 25% reduction in the risk of invasive disease corresponding to a hazard ratio of 0.75 when the risk is calculated relative to patients not receiving the treatment. 105. The method of any one of embodiments 1 to 104, wherein the treatment reduces the risk of invasive disease to a similar level for patient subgroups comprising patients with stage II early breast cancer, stage III early breast cancer, patients who are premenopausal women or men, and patients who are postmenopausal women. 106. The method of any one of embodiments 1 to 105, wherein the treatment yields no deterioration in overall survival corresponding to a hazard ratio of 0.76 when the risk is calculated relative to patients not receiving the treatment. 107. The method of one of embodiments 1 to 106, wherein the treatment reduces and / or prevents one or more of recurrence of the cancer, spread of the cancer, development and / or growth of an additional cancer, and risk of death from the cancer. PAT059494-WO-PCT 108. The method of embodiment 107, wherein the treatment reduces the recurrence of cancer, wherein the recurrence is one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, and distant recurrence. 109. The method of embodiment 107 or embodiment 108, wherein the treatment reduces the spread of cancer, wherein the spread of cancer is an invasive contralateral breast cancer or an additional primary invasive cancer. 110. The method of any one of embodiments 1 to 109, wherein the treatment prevents death from cancer. 111. A method of maintaining in remission an adult patient who had previously been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient a treatment comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28- day cycle in combination with an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle. 112. A method of preventing breast cancer recurrence in an adult patient, comprising providing adjuvant treatment to a patient who has received a prior treatment for HR+ / HER2- stage II or III early breast cancer, wherein the adjuvant treatment comprises administering to the patient 400 mg ribociclib or a pharmaceutically acceptable salt thereof on days 1 to 21 of a 28-day cycle for at least 36 months, in combination with an aromatase inhibitor as defined in any one of embodiments 26 to 31 administered on every day of the 28-day cycle. 113. The method of embodiment 112, wherein the prior treatment is surgical resection of the cancer. 114. Ribociclib or a pharmaceutically acceptable salt thereof and an aromatase inhibitor for use in a method of treatment for HR+ / HER2- stage II or III early breast cancer in an adult patient, wherein the method is the method of any one of embodiments 1 to 112. 115. The use of ribociclib or a pharmaceutically acceptable salt thereof and an aromatase inhibitor in the manufacture of a medicament for treating HR+ / HER2- stage II or III early breast cancer in an adult patient, wherein the medicament is administered by the method of any one of embodiments 1 to 112. 116. A kit for performing a method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient according to any one of embodiments 1 to 112. PAT059494-WO-PCT 117. A method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient in remission, comprising administering to the adult patient ribociclib in combination with an aromatase inhibitor whereby the administration maintains the adult patient in remission for at least 3 months. 118. A method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient, comprising providing adjuvant treatment by administering ribociclib in combination with aromatase inhibitor, wherein the patient at start of the adjuvant treatment is in complete remission, and the administration of ribociclib in combination with aromatase inhibitor maintains the adult patient in complete remission for at least 3 months. 119. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 6 months. 120. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 9 months. 121. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 12 months. 122. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 15 months. 123. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 18 months. 124. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 21 months. 125. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 24 months. 126. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 27 months. 127. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 30 months. 128. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 33 months. PAT059494-WO-PCT 129. The method of embodiment 117 or 118, wherein the administration maintains the adult patient in remission (e.g., complete remission) for at least 36 months. 130. The method of any one of embodiments 117 to 129, wherein ribociclib and aromatase inhibitor are administered for a treatment duration, and the administration maintains the adult patient in remission (e.g., complete remission) for at least the treatment duration. 131. The method of any one of embodiments 117 to 129, wherein a dose of 400 mg ribociclib is orally administered once daily on days 1-21 of a 28-day cycle and aromatase inhibitor is administered once daily on each day of the 28-day cycle. 132. The method of any one of embodiments 117 to 129, wherein a dose of 400 mg ribociclib is orally administered once daily on days 1-21 of a 28-day cycle for a treatment duration of up to three years and aromatase inhibitor is administered once daily on each day of the 28-day cycle for the up to three years. 133. The method of any one of embodiments 117 to 129, wherein a dose of 400 mg ribociclib is orally administered once daily on days 1-21 of a 28-day cycle for a treatment duration of up to five years and aromatase inhibitor is administered once daily on each day of the 28-day cycle for the up to five years. 134. The method of any one of embodiments 117 to 133, wherein a pharmaceutically acceptable salt of ribociclib is orally administered in an amount corresponding to 400 mg ribociclib. 135. The method of embodiment 134, wherein the pharmaceutically acceptable salt is ribociclib succinate. 136. The method of any one of embodiments 117 to 135, wherein the adult patient was never treated with a 600 mg dose of ribociclib. 137. The method of any one of embodiments 117 to 136, wherein the adult patient has never been diagnosed with HR+ / HER2- advanced or metastatic breast cancer. 138. The method of any one of embodiments 117 to 137, wherein ribociclib and aromatase inhibitor are administered as adjuvant therapy. 139. The method of embodiment any one of embodiments 117 to 138, wherein the ribociclib is not administered at a dose of 600 mg / day. 140. The method of any one of embodiments 117 to 139, wherein the dose of ribociclib is administered in tablet form. PAT059494-WO-PCT 141. The method of any one of embodiments 117 to 139, wherein two tablets are orally administered to the adult patient once daily on days 1-21 of a 28-day cycle repeating for a treatment duration, and each tablet contains an amount of a pharmaceutically acceptable ribociclib salt corresponding to 200 mg ribociclib. 142. The method of embodiment 141, wherein the ribociclib salt is ribociclib succinate. 143. The method of any one of embodiments 117 to 142, wherein the aromatase inhibitor is letrozole. 144. The method of any one of embodiments 117 to 142, wherein the aromatase inhibitor is anastrazole. 145. The method of any one of embodiments 117 to 144, wherein the aromatase inhibitor is letrozole, and the letrozole is administered in a dose ranging from 1 mg to 4 mg once daily. 146. The method of any one of embodiments 117 to 144, the aromatase inhibitor is letrozole, and the letrozole is administered in a dose of 2.5 mg once daily. 147. The method of any one of embodiments 117 to 144, wherein the aromatase inhibitor is anastrozole, and the anastrozole is administered in a dose ranging from 0.5 mg once daily to 1.5 mg once daily. 148. The method of any one of embodiments 117 to 144, wherein the aromatase inhibitor is anastrozole, and the anastrozole is administered in a dose of 1mg once daily. 149. The method of any one of embodiments 114 to 148, further comprising administering to the adult patient a gonadotropin-releasing hormone agonist. 150. The method of embodiment 149, wherein the gonadotropin-releasing hormone agonist is goserelin. 151. The method of embodiment 150, wherein the goserelin is administered in a dose ranging from 2 mg to 5 mg. 152. The method of embodiment 151, wherein the dose of goserelin is 3.6 mg. 153. The method of any one of embodiments 150 to 152, wherein the goserelin is administered subcutaneously. 154. The method of any one of embodiments 150 to 153, wherein the goserelin is administered once every 4 weeks. PAT059494-WO-PCT 155. The method of any one of embodiments 117 to 148, wherein the patient is a postmenopausal woman. 156. The method of any one of embodiments 117 to 154, wherein the patient is a premenopausal woman or a man. 157. The method of any one of embodiments 117 to 156, wherein the breast cancer has a histological subtype that is ductal or a histological subtype that is lobular. 158. The method of any one of embodiments 117 to 156, wherein the breast cancer is a stage IIA cancer or a stage IIB cancer. 159. The method of any one of embodiments 117 to 156, wherein the breast cancer is a stage IIA cancer. 160. The method of any one of embodiments 117 to 156, wherein the breast cancer is a stage IIB cancer. 161. The method of any one of embodiments 117 to 156, wherein the breast cancer is a stage IIIA cancer, a stage IIIB cancer, or a stage IIIC cancer. 162. The method of any one of embodiments 117 to 156, wherein the breast cancer is a stage IIIA cancer. 163. The method of any one of embodiments 117 to 156, wherein the breast cancer is a stage IIIB cancer. 164. The method of any one of embodiments 117 to 156, wherein the breast cancer is a stage IIIC cancer. 165. The method of any one of embodiments 117 to 156, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 166. The method of any one of embodiments 117 to 156, wherein treatment with ribociclib and aromatase inhibitor is not adjusted on the basis of the nodal status of the early breast cancer. 167. The method of any one of embodiments 117 to 156, wherein the breast cancer has a nodal status selected from N0, N1, N2, and N3. 168. The method of any one of embodiments 117 to 156, wherein the breast cancer has a nodal status of N0. PAT059494-WO-PCT 169. The method of any one of embodiments 117 to 156, wherein the breast cancer has a nodal status of N1-N3. 170. The method of any one of embodiments 117 to 156, wherein the breast cancer has a nodal status of N1. 171. The method of any one of embodiments 117 to 156, wherein the breast cancer has a nodal status of N2. 172. The method of any one of embodiments 117 to 156, wherein the breast cancer has a nodal status of N3. 173. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises one or more cells having a histological grade selected from G1, G2, or G3. 174. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises one or more cells having the histological grade G1. 175. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises one or more cells having the histological grade G2. 176. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises one or more cells having the histological grade G3. 177. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises a tumor of category T0, T1, T2, T3, or T4. 178. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises a tumor of category T1, T2, or T3. 179. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises a tumor of category T0. 180. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises a tumor of category T1. 181. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises a tumor of category T2. 182. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises a tumor of category T3. PAT059494-WO-PCT 183. The method of any one of embodiments 117 to 156, wherein the breast cancer comprises a tumor of category T4. 184. The method of any one of embodiments 117 to 156, wherein the breast cancer has a Ki67 status of 20 or lower. 185. The method of any one of embodiments 117 to 156, wherein the breast cancer has a Ki67 status of greater than 20. 186. The method of any one of embodiments 117 to 185, wherein prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had surgery for the early breast cancer. 187. The method of any one of embodiments 117 to 185, wherein prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had (1) surgery for the early breast cancer, followed by (2) chemotherapy. 188. The method of any one of embodiments 117 to 185, wherein prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had (1) surgery for the early breast cancer, followed by (2) chemotherapy and / or endocrine therapy. 189. The method of embodiment 188, wherein the endocrine therapy was therapy with a prior aromatase inhibitor. 190. The method of embodiment 188, wherein the prior aromatase inhibitor was letrozole or anastrozole. 191. The method of any one of embodiments 117 to 185, wherein immediately prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had surgery for the early breast cancer. 192. The method of any one of embodiments 186 to 191, wherein the surgery comprised a complete surgical resection of the cancer. 193. The method of any one of embodiments 186 to 191, wherein the surgery was a mastectomy. 194. The method of any one of embodiments 186 to 191, wherein the patient received neoadjuvant therapy. 195. The method of embodiment 194, wherein the neoadjuvant therapy was chemotherapy. PAT059494-WO-PCT 196. The method of any one of embodiments 117 to 195, wherein the adult patient is located in a geographic region selected from North America, Western Europe, or Oceania. 197. The method of any one of embodiments 117 to 195, wherein the patient is Asian. 198. The method of any one of embodiments 117 to 195, wherein the patient is 18 to 45 years of age. 199. The method of any one of embodiments 117 to 195, wherein the patient is 45 to 54 years of age. 200. The method of any one of embodiments 117 to 195, wherein the patient is 54 to 64 years of age. 201. The method of any one of embodiments 117 to 195, wherein the patient is greater than 64 years of age. 202. The method of any one of embodiments 117 to 195, wherein the patient has a BMI of 25 or higher. 203. The method of any one of embodiments 117 to 195, wherein the patient has a BMI lower than 25. 204. The method of any one of embodiments 117 to 203, wherein the treatment improves a condition of the patient relative to a patient not receiving the treatment and / or relative to the condition in the patient prior to treatment. 205. The method of any one of embodiments 117 to 203, wherein the treatment reduces the risk of invasive disease. 206. The method of any one of embodiments 117 to 203, wherein the treatment reduces the risk of invasive disease in the adult patient corresponding to a hazard ratio of less than 1 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. 207. The method any one of embodiments 117 to 203, wherein the treatment reduces the risk of invasive disease in the adult patient corresponding to a hazard ratio of less than or equal to 0.78 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. PAT059494-WO-PCT The method of any one of embodiments 117 to 203, wherein the adult patient is a premenopausal woman or a man and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.72 when the risk is calculated relative to other premenopausal women or men, respectively, having received the same treatment as the premenopausal woman or man, respectively, except that the other premenopausal women or men did not receive the ribociclib. The method of any one of embodiments 117 to 203, wherein the adult patient was diagnosed with HR+ / HER2- stage III early breast cancer and the treatment reduces the risk of invasive disease in the adult patient corresponding to a hazard ratio of less than or equal to 0.74 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. The method of any one of embodiments 117 to 203, wherein the adult patient was diagnosed with HR+ / HER2- stage II early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.76 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. The method of any one of embodiments 117 to 203, wherein the adult patient was diagnosed with HR+ / HER2- stage III early breast cancer, and the treatment yields at least a 25% reduction in the risk of invasive disease corresponding to a hazard ratio of 0.75 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. The method of any one of embodiments 117 to 203, wherein the treatment reduces the risk of invasive disease to a similar level for patient subgroups comprising patients with stage II early breast cancer, stage III early breast cancer, patients who are premenopausal women or men, and patients who are postmenopausal women. The method of any one of embodiments 117 to 203, wherein the treatment yields no deterioration in overall survival corresponding to a hazard ratio of 0.76 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib. The method of one of embodiments 117 to 203, wherein the treatment reduces and / or prevents one or more of recurrence of the cancer, spread of the cancer, development and / or growth of an additional cancer, and risk of death from the cancer. PAT059494-WO-PCT 215. The method of one of embodiments 117 to 203, wherein the treatment reduces the recurrence of cancer, wherein the recurrence is one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, and distant recurrence. 216. The method of one of embodiments 117 to 203, wherein the treatment reduces the spread of cancer, wherein the spread of cancer is an invasive contralateral breast cancer or an additional primary invasive cancer. 217. Ribociclib or a pharmaceutically acceptable salt thereof and an aromatase inhibitor for use in a method of treatment for HR+ / HER2- stage II or III early breast cancer in an adult patient, wherein the method is the method of any one of embodiments 117 to 216. 218. The use of ribociclib or a pharmaceutically acceptable salt thereof and an aromatase inhibitor in the manufacture of a medicament for treating HR+ / HER2- stage II or III early breast cancer in an adult patient, wherein the medicament is administered by the method of any one of embodiments 117 to 216. 219. A kit for performing a method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient according to any one of embodiments 117 to 216. 220. A method of treating an adult patient who has been diagnosed with HER+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle, wherein the method results in an improvement in the patient in one or more of their overall survival (OS), distant disease- free survival (DDFS), or recurrence free survival (RFS). 221. A method for improving one or more of overall survival (OS), distant disease-free survival (DDFS), or recurrence free survival (RFS) in a patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 222. A method for reducing the risk of local or regional invasive recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered PAT059494-WO-PCT on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 223. A method for reducing the risk of invasive recurrence of early breast cancer in one or more of the bone, liver, and lung or pleura of an adult patient, who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 224. The method of any of embodiments 220 to 223, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 225. A method for reducing the risk of recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle and (ii) an aromatase inhibitor administered on every day of the 28-day cycle, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 226. The method of any of embodiments 220 to 225, wherein the breast cancer has a nodal status of N0, N1, N2 or N3. 227. The method of embodiment 226, wherein the breast cancer has a nodal status of N0. 228. The method of any of embodiments 220 to 227, wherein the early breast cancer is stage II, for example stage IIA. 229. The method of any of embodiments 220 to 227, wherein the early breast cancer is stage III, for example stage IIIB or IIIC. 230. The method of any of embodiments 220 to 229, wherein the breast cancer is of the ductal subtype. 231. The method of any of embodiments 220 to 230, wherein the patient is Asian. 232. The method of any of embodiments 220 to 231, wherein the method is an adjuvant treatment because the patient has received at least one prior treatment for breast cancer selected from the group consisting of surgery, chemotherapy, and radiation therapy. 233. The method of embodiment 232, wherein the patient has not had a mastectomy. PAT059494-WO-PCT 234. The method of any of embodiments 220 to 233, wherein the dose of ribociclib is 400 mg / day. 235. The method of any of embodiments 220 to 234, wherein the ribociclib is administered in the form of a salt, preferably as ribociclib succinate. 236. The method of any of embodiments 220 to 235, wherein the aromatase inhibitor is letrozole or anastrozole. 237. The method of embodiment 236, wherein the aromatase inhibitor is letrozole, preferably administered in a dose of 2.5 mg / day. 238. The method of embodiment 236, wherein the aromatase inhibitor is anastrozole, preferably administered in a dose of 1 mg / day. 239. The method of any of embodiments 220 to 238, wherein the dose of ribociclib is 400 mg / day, the ribociclib is administered in the form of ribociclib succinate, and the aromatase inhibitor is letrozole or anastrozole, preferably 2.5 mg / day of letrozole or 1 mg / day anastrozole. 240. The method of any of embodiments 220 to 239, wherein the improvement in OS, DDFS and / or RFS, or the reduction in the risk of recurrence of the breast cancer, are achieved in the patient for at least 36 months. 241. Ribociclib for use in a method of improving one or more of overall survival (OS), distant disease-free survival (DDFS), or recurrence free survival (RFS) in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 242. Ribociclib for use in a method of reducing the risk of local or regional invasive recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 243. Ribociclib for use in a method of reducing the risk of invasive recurrence of early breast cancer in one or more of the bone, liver, and lung or pleura of an adult patient who has PAT059494-WO-PCT been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 244. Ribociclib for use in accordance with any of embodiments 241 to 243, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 245. Ribociclib for use in a method of reducing the risk of recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1- 21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28- day cycle, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 246. Ribociclib for use according to any of embodiments 241 to 245, wherein the breast cancer has a nodal status of N0, N1, N2 or N3. 247. Ribociclib for use according to embodiment 246, wherein the breast cancer has a nodal status of N0. 248. Ribociclib for use according to any of embodiments 241 to 247, wherein the early breast cancer is stage II, such as stage IIA. 249. Ribociclib for use according to any of embodiments 241 to 247, wherein the early breast cancer is stage III, such as stage IIIB or IIIC. 250. Ribociclib for use according to any of embodiments 241 to 249, wherein the breast cancer is of the ductal subtype. 251. Ribociclib for use according to any of embodiments 241 to 250, wherein the patient is Asian. 252. Ribociclib for use according to any of embodiments 241 to 251, wherein the method is an adjuvant treatment because the patient has received at least one prior treatment for breast cancer selected from the group consisting of surgery, chemotherapy, and radiation therapy. PAT059494-WO-PCT 253. Ribociclib for use according to embodiment 252, wherein the patient has not had a mastectomy. 254. Ribociclib for use according to any of embodiments 241 to 253, wherein the dose of ribociclib is 400 mg / day. 255. Ribociclib for use according to any of embodiments 241 to 254, wherein the ribociclib is administered in the form of a salt, preferably as ribociclib succinate. 256. Ribociclib for use according to any of embodiments 241 to 255, wherein the aromatase inhibitor is letrozole or anastrozole. 257. Ribociclib for use according to embodiment 256, wherein the aromatase inhibitor is letrozole, preferably administered in a dose of 2.5 mg / day. 258. Ribociclib for use according to embodiment 256, wherein the aromatase inhibitor is anastrozole, preferably administered in a dose of 1 mg / day. 259. Ribociclib for use according to any of embodiments 241 to 258, wherein the dose of ribociclib is 400 mg / day, the ribociclib is administered in the form of ribociclib succinate, and the aromatase inhibitor is letrozole or anastrozole, preferably 2.5 mg / day of letrozole or 1 mg / day anastrozole. 260. Ribociclib for use according to any of embodiments 241 to 259, wherein the improvement in OS, DDFS and / or RFS, or the reduction in the risk of recurrence of the breast cancer, are achieved in the patient for at least 36 months. 261. Ribociclib succinate for use in a method of treatment of HR+ / HER2- stage II or stage III early breast cancer in an adult patient who has received at least one prior treatment for early breast cancer and has no signs or symptoms of cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1 to 21 of a 28-day cycle, and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle. 262. Ribociclib succinate for use according to embodiment 261, wherein the adjuvant treatment comprises a dose of 2.5 mg / day letrozole. 263. Ribociclib succinate for use according to embodiment 261, wherein the adjuvant treatment comprises a dose of 1 mg / day anastrozole. PAT059494-WO-PCT 264. Ribociclib succinate for use according to any one of embodiments 261 to 263, wherein the breast cancer has a nodal status of N0, N1, N2 or N3. 265. Ribociclib succinate for use according to embodiment 264, wherein the breast cancer has a nodal status of N0. 266. Ribociclib succinate for use according to any one of embodiments 261 to 265, wherein the early breast cancer is stage II, such as stage IIA. 267. Ribociclib succinate for use according to any one of embodiments 261 to 265, wherein the early breast cancer is stage III, such as stage IIIB. 268. Ribociclib succinate for use according to any one of embodiments 261 to 265, wherein the early breast cancer is stage III, such as IIIC. 269. Ribociclib succinate for use according to any one of embodiments 261 to 268, wherein the breast cancer is of the ductal subtype. 270. Ribociclib succinate for use according to any one of embodiments 261 to 269, wherein the patient is Asian. 271. Ribociclib succinate for use according to any one of embodiments 261 to 270, wherein the method is an adjuvant treatment because the patient has received at least one prior treatment for breast cancer selected from the group consisting of surgery, chemotherapy, endocrine therapy, and radiation therapy. 272. Ribociclib succinate for use according to embodiment 271, wherein the patient has not had a mastectomy. 273. Ribociclib succinate for use according to any one of embodiments 261 to 272, wherein the method improves overall survival (OS), distant disease-free survival (DDFS), and / or recurrence free survival (RFS) of the breast cancer in the patient for at least 36 months; or the method reduces the risk of recurrence of the breast cancer in the patient for at least 36 months. 274. A method of preventing recurrence of breast cancer in an adult patient who has received a prior treatment for HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, and (ii) a dose of an aromatase inhibitor, preferably letrozole or anastrozole. PAT059494-WO-PCT 275. A method of treating an adult patient in remission from HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, and (ii) a dose of an aromatase inhibitor, preferably letrozole or anastrozole. 276. A method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient in need thereof, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle and (ii) an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle. 277. The method of any one of embodiments 274 to 276, wherein the ribociclib is a pharmaceutically acceptable ribociclib salt. 278. The method of embodiment 277, wherein the ribociclib salt is ribociclib succinate. 279. The method of any one of embodiments 274, 275, 277, and 278, wherein the dose of ribociclib is not 600 mg / day. 280. The method of any one of embodiments 274 to 278, wherein the dose of ribociclib is 200 mg / day or 400 mg / day. 281. The method of embodiment 280, wherein ribociclib is administered as ribociclib succinate, and the total dose of ribociclib is 200 mg / day. 282. The method of embodiment 280, wherein ribociclib is administered as ribociclib succinate, and the total dose of ribociclib is 400 mg / day. 283. The method of embodiment 280, wherein the ribociclib is administered at a dose of 400 mg / day for a period of time, after which a dose of 200 mg / day ribociclib is administered. 284. The method of any one of embodiments 274 to 283, wherein the dose of ribociclib is administered orally. 285. The method of any one of embodiments 274 to 284, wherein the dose of ribociclib is administered in tablet form. 286. The method of any one of embodiments 274 to 285, wherein the aromatase inhibitor is letrozole or anastrozole. 287. The method of any one of embodiments 274 to 286, wherein the aromatase inhibitor is administered orally. PAT059494-WO-PCT 288. The method of embodiment 286 or 287, wherein the letrozole is administered in a dose ranging from 1 mg / day to 4 mg / day. 289. The method of embodiment 288, wherein the letrozole is administered in a dose of 2.5 mg / day. 290. The method of embodiment 286 or 287, wherein the anastrozole is administered in a dose ranging from 0.5 mg / day to 1.5 mg / day. 291. The method of embodiment 290, wherein the anastrozole is administered in a dose of 1 mg / day. 292. A method of treating breast cancer recurrence in an adult patient who has received at least one prior treatment for HR+ / HER2- stage II or III early breast cancer and who has no detectable signs or symptoms of breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1 to 21 of a 28-day cycle, and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle. 293. A method of treating an adult patient who is in remission from HR+ / HER2- stage II or stage III early breast cancer and in need of adjuvant treatment, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1-21 of a 28-day cycle and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle. 294. The method of any one of embodiments 274 to 293, wherein the treatment further comprises administering a gonadotropin-releasing hormone agonist. 295. The method of embodiment 294, wherein the gonadotropin-releasing hormone agonist is goserelin. 296. The method of embodiment 295, wherein the goserelin is administered in a dose ranging from 2 mg to 5 mg. 297. The method of embodiment 296, wherein the dose of goserelin is 3.6 mg. 298. The method of any one of embodiments 294 to 297, wherein the goserelin is administered subcutaneously. 299. The method of any one of embodiments 294 to 298, wherein the goserelin is administered once every 4 weeks. PAT059494-WO-PCT 300. The method of any one of embodiments 274 to 299, wherein the patient is a postmenopausal woman. 301. The method of any one of embodiments 274 to 293, wherein the patient is a premenopausal woman or a man. 302. The method of any one of embodiments 274 to 301, wherein the treatment is administered to the patient for at least 12 months. 303. The method of embodiment 302, wherein the treatment is administered to the patient for at least 24 months. 304. The method of embodiment 302 or 303, wherein the treatment is administered to the patient for at least 36 months. 305. The method of any one of embodiments 302 to 304, wherein the treatment is administered to the patient for at least 48 months. 306. The method of any one of embodiments 302 to 305, wherein the treatment is administered to the patient for at least 60 months. 307. The method of any one of embodiments 274 to 306, wherein the breast cancer is ER+ and PR+. 308. The method of any one of embodiments 274 to 306, wherein the breast cancer is ER- and PR+. 309. The method of any one of embodiments 274 to 306, wherein the breast cancer is ER+ and PR-. 310. The method of any one of embodiments 274 to 309, wherein the breast cancer has a histological subtype that is ductal. 311. The method of any one of embodiments 274 to 310, wherein the breast cancer has a histological subtype that is lobular. 312. The method of any one of embodiments 274 to 311, wherein the breast cancer is a stage IIA cancer or a stage IIB cancer. 313. The method of embodiment 312, wherein the breast cancer is a stage IIA cancer. 314. The method of embodiment 312, wherein the breast cancer is a stage IIB cancer. 315. The method of any one of embodiments 274 to 311, wherein the breast cancer is a stage IIIA cancer, a stage IIIB cancer, or a stage IIIC cancer. PAT059494-WO-PCT 316. The method of embodiment 315, wherein the breast cancer is a stage IIIA cancer. 317. The method of embodiment 315, wherein the breast cancer is a stage IIIB cancer. 318. The method of embodiment 315, wherein the breast cancer is a stage IIIC cancer. 319. The method of any one of embodiments 274 to 318, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 320. The method of any one of embodiments 274 to 319, wherein the breast cancer has a nodal status selected from N0, N1, N2, and N3. 321. The method of embodiment 319 or 320, wherein the breast cancer has a nodal status of N0. 322. The method of embodiment 319 or 320, wherein the breast cancer has a nodal status of N1 to N3. 323. The method of embodiment 319 or 320, wherein the breast cancer has a nodal status of N1. 324. The method of embodiment 319 or 320, wherein the breast cancer has a nodal status of N2. 325. The method of embodiment 319 or 320, wherein the breast cancer has a nodal status of N3. 326. The method of any one of embodiments 274 to 325, wherein the breast cancer comprises one or more cells having a histological grade selected from G1, G2, or G3. 327. The method of embodiment 326, wherein the breast cancer comprises one or more cells having the histological grade G1. 328. The method of embodiment 326, wherein the breast cancer comprises one or more cells having the histological grade G2. 329. The method of embodiment 326, wherein the breast cancer comprises one or more cells having the histological grade G3. 330. The method of any one of embodiments 274 to 329, wherein the breast cancer comprises a tumor of category T0, T1, T2, T3, or T4. 331. The method of embodiment 330, wherein the breast cancer comprises a tumor of category T1, T2, or T3. PAT059494-WO-PCT 332. The method of embodiment 330, wherein the breast cancer comprises a tumor of category T0. 333. The method of embodiment 330 or embodiment 331, wherein the breast cancer comprises a tumor of category T1. 334. The method of embodiment 330 or embodiment 331, wherein the breast cancer comprises a tumor of category T2. 335. The method of embodiment 330 or embodiment 331, wherein the breast cancer comprises a tumor of category T3. 336. The method of embodiment 330, wherein the breast cancer comprises a tumor of category T4. 337. The method of any one of embodiments 274 to 336, wherein the breast cancer has a Ki67 status of 20 or lower. 338. The method of any one of embodiments 274 to 336, wherein the breast cancer has a Ki67 status of greater than 20. 339. The method of any one of embodiments 274 to 338, wherein prior to the administration, the patient has received a loading dose of (i) ribociclib and / or (ii) an endocrine therapy. 340. The method of any one of embodiments 274 to 291 and 293 to 339, wherein the patient has received at least one prior treatment for cancer. 341. The method of embodiment 292 or embodiment 340, wherein the prior treatment is an adjuvant treatment after another prior treatment. 342. The method of embodiment 340 or 341, wherein the prior treatment is surgery. 343. The method of embodiment 342, wherein the surgery comprises a complete surgical resection of the cancer. 344. The method of embodiment 342 or embodiment 343, wherein the surgery is a mastectomy. 345. The method of embodiment 340 or embodiment 341, wherein the prior treatment is a chemotherapy. 346. The method of embodiment 345, wherein the prior treatment is an adjuvant chemotherapy. 347. The method of embodiment 345, wherein the prior treatment is a neoadjuvant chemotherapy. PAT059494-WO-PCT 348. The method of embodiment 340 or embodiment 341, wherein the prior treatment is an endocrine therapy. 349. The method of embodiment 340 or embodiment 341, wherein the prior treatment is radiation therapy. 350. The method of any one of embodiments 292 and 340 to 349, wherein the patient did not respond to the prior treatment. 351. The method of any one of embodiments 274 to 350, wherein the patient is located in a geographic region selected from North America, Western Europe, or Oceania. 352. The method of any one of embodiments 274 to 351, wherein the patient is Asian. 353. The method of any one of embodiments 274 to 352, wherein the patient is 18 to 45 years of age. 354. The method of any one of embodiments 274 to 352, wherein the patient is 45 to 54 years of age. 355. The method of any one of embodiments 274 to 352, wherein the patient is 54 to 64 years of age. 356. The method of any one of embodiments 274 to 352, wherein the patient is greater than 64 years of age. 357. The method of any one of embodiments 274 to 357, wherein the patient has a BMI of 25 or higher. 358. The method of any one of embodiments 274 to 357, wherein the patient has a BMI lower than 25. 359. The method of any one of embodiments 274 to 358, wherein the treatment improves a condition of the patient relative to a patient not receiving the treatment and / or relative to the condition in the patient prior to treatment. 360. The method of any one of embodiments 274 to 359, wherein the treatment reduces the risk of invasive disease. 361. The method of embodiment 360, wherein the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than 1 when the risk is calculated relative to patients not receiving the treatment. PAT059494-WO-PCT 362. The method of embodiment 361, wherein the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.78 when the risk is calculated relative to patients not receiving the treatment. 363. The method of any one of embodiments 274 to 299 and 301 to 362, wherein the patient is a premenopausal woman or a man and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.72 when the risk is calculated relative to patients receiving the treatment. 364. The method of any one of embodiments 360 to 362, wherein the cancer is HR+ / HER2- stage III early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.74 when the risk is calculated relative to patients not receiving the treatment. 365. The method of any one of embodiments 360 to 362, wherein the cancer is HR+ / HER2- stage II early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.76 when the risk is calculated relative to patients not receiving the treatment. 366. The method of any one of embodiments 360 to 362, wherein the cancer is HR+ / HER2- stage III early breast cancer, and the treatment yields at least a 25% reduction in the risk of invasive disease corresponding to a hazard ratio of 0.75 when the risk is calculated relative to patients not receiving the treatment. 367. The method of any one of embodiments 360 to 366, wherein the treatment reduces the risk of invasive disease to a similar level for patient subgroups comprising patients with stage II early breast cancer, stage III early breast cancer, patients who are premenopausal women or men, and patients who are postmenopausal women. 368. The method of any one of embodiments 274 to 367, wherein the treatment yields no deterioration in overall survival corresponding to a hazard ratio of 0.76 when the risk is calculated relative to patients not receiving the treatment. 369. The method of any one of embodiments 274 to 368, wherein the treatment reduces and / or prevents one or more of recurrence of the cancer, spread of the cancer, development and / or growth of an additional cancer, and risk of death from the cancer. 370. The method of embodiment 369, wherein the treatment reduces the recurrence of cancer, wherein the recurrence is one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, and distant recurrence. PAT059494-WO-PCT 371. The method of embodiment 369, wherein the treatment reduces the spread of cancer, wherein the spread of cancer is an invasive contralateral breast cancer or an additional primary invasive cancer. 372. The method of any one of embodiments 274 to 371, wherein the treatment prevents death from cancer. J. Further exemplary embodiments Further methods of treatment and uses of ribociclib are provided in the following embodiments. 1. A method of treating an adult patient who has been diagnosed with HER+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant therapy comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle, wherein the method results in an improvement in the patient in one or more of their overall survival (OS), distant disease-free survival (DDFS), or recurrence free survival (RFS). 2. A method for improving one or more of overall survival (OS), distant disease-free survival (DDFS), or recurrence free survival (RFS) in a patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 3. A method for reducing the risk of local or regional invasive recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycleand (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 4. A method for reducing the risk of invasive recurrence of early breast cancer in one or more of the bone, liver, and lung or pleura of an adult patient, who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. PAT059494-WO-PCT 5. The method of any of claims 1 to 4, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 6. A method for reducing the risk of recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle and (ii) an aromatase inhibitor administered on every day of the 28-day cycle, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 7. The method of any of claims 1 to 6, wherein the breast cancer has a nodal status of N0, N1, N2 or N3. 8. The method of claim 7, wherein the breast cancer has a nodal status of N0. 9. The method of any of claims 1 to 8, wherein the early breast cancer is stage II, for example stage IIA. 10. The method of any of claims 1 to 8, wherein the early breast cancer is stage III, for example stage IIIB or IIIC. 11. The method of any of claims 1 to 10, wherein the breast cancer is of the ductal subtype. 12. The method of any of claims 1 to 11, wherein the patient is Asian. 13. The method of any of claims 1 to 12, wherein the method is an adjuvant treatment because the patient has received at least one prior treatment for breast cancer selected from the group consisting of surgery, chemotherapy, and radiation therapy. 14. The method of claim 13, wherein the patient has not had a mastectomy. 15. The method of any of claims 1 to 14, wherein the dose of ribociclib is 400 mg / day. 16. The method of any of claims 1 to 15, wherein the ribociclib is administered in the form of a salt, preferably as ribociclib succinate. 17. The method of any of claims 1 to 16, wherein the aromatase inhibitor is letrozole or anastrozole. 18. The method of claim 17, wherein the aromatase inhibitor is letrozole, preferably administered in a dose of 2.5 mg / day. PAT059494-WO-PCT 19. The method of claim 17, wherein the aromatase inhibitor is anastrozole, preferably administered in a dose of 1 mg / day. 20. The method of any of claims 1 to 19, wherein the dose of ribociclib is 400 mg / day, the ribociclib is administered in the form of ribociclib succinate, and the aromatase inhibitor is letrozole or anastrozole, preferably 2.5 mg / day of letrozole or 1 mg / day anastrozole. 21. The method of any of claims 1 to 20, wherein the improvement in OS, DDFS and / or RFS, or the reduction in the risk of recurrence of the breast cancer, are achieved in the patient for at least 36 months. 22. Ribociclib for use in a method of improving one or more of overall survival (OS), distant disease-free survival (DDFS), or recurrence free survival (RFS) in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 23. Ribociclib for use in a method of reducing the risk of local or regional invasive recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising g administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 24. Ribociclib for use in a method of reducing the risk of invasive recurrence of early breast cancer in one or more of the bone, liver, and lung or pleura of an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer and the method is an adjuvant treatment comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle. 25. Ribociclib for use in accordance with any of claims 22 to 24, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 26. Ribociclib for use in a method of reducing the risk of recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a PAT059494-WO-PCT 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 27. Ribociclib for use according to any of claims 22 to 26, wherein the breast cancer has a nodal status of N0, N1, N2 or N3. 28. Ribociclib for use according to claim 27, wherein the breast cancer has a nodal status of N0. 29. Ribociclib for use according to any of claims 22 to 28, wherein the early breast cancer is stage II, such as stage IIA. 30. Ribociclib for use according to any of claims 22 to 28, wherein the early breast cancer is stage III, such as stage IIIB or IIIC. 31. Ribociclib for use according to any of claims 22 to 30, wherein the breast cancer is of the ductal subtype. 32. Ribociclib for use according to any of claims 22 to 31, wherein the patient is Asian. 33. Ribociclib for use according to any of claims 22 to 32, wherein the method is an adjuvant treatment because the patient has received at least one prior treatment for breast cancer selected from the group consisting of surgery, chemotherapy, and radiation therapy. 34. Ribociclib for use according to claim 33, wherein the patient has not had a mastectomy. 35. Ribociclib for use according to any of claims 22 to 34, wherein the dose of ribociclib is 400 mg / day. 36. Ribociclib for use according to any of claims 22 to 35, wherein the ribociclib is administered in the form of a salt, preferably as ribociclib succinate. 37. Ribociclib for use according to any of claims 22 to 36, wherein the aromatase inhibitor is letrozole or anastrozole. 38. Ribociclib for use according to claim 37, wherein the aromatase inhibitor is letrozole, preferably administered in a dose of 2.5 mg / day. 39. Ribociclib for use according to claim 37, wherein the aromatase inhibitor is anastrozole, preferably administered in a dose of 1 mg / day. PAT059494-WO-PCT 40. Ribociclib for use according to any of claims 22 to 39, wherein the dose of ribociclib is 400 mg / day, the ribociclib is administered in the form of ribociclib succinate, and the aromatase inhibitor is letrozole or anastrozole, preferably 2.5 mg / day of letrozole or 1 mg / day anastrozole. 41. Ribociclib for use according to any of claims 22 to 40, wherein the improvement in OS, DDFS and / or RFS, or the reduction in the risk of recurrence of the breast cancer, are achieved in the patient for at least 36 months. K. More exemplary embodiments More methods of treatment and uses of ribociclib are provided in the following embodiments. 1. Ribociclib succinate for use in a method of treatment of HR+ / HER2- stage II or stage III early breast cancer in an adult patient who has received at least one prior treatment for early breast cancer and has no signs or symptoms of cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1 to 21 of a 28-day cycle, and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle. 2. Ribociclib succinate for use according to embodiment 1, wherein the adjuvant treatment comprises a dose of 2.5 mg / day letrozole. 3. Ribociclib succinate for use according to embodiment 1, wherein the adjuvant treatment comprises a dose of 1 mg / day anastrozole. 4. Ribociclib succinate for use according to any one of embodiments 1 to 3, wherein the breast cancer has a nodal status of N0, N1, N2 or N3. 5. Ribociclib succinate for use according to embodiment 4, wherein the breast cancer has a nodal status of N0. 6. Ribociclib succinate for use according to any one of embodiments 1 to 5, wherein the early breast cancer is stage II, such as stage IIA. 7. Ribociclib succinate for use according to any one of embodiments 1 to 5, wherein the early breast cancer is stage III, such as stage IIIB. 8. Ribociclib succinate for use according to any one of embodiments 1 to 5, wherein the early breast cancer is stage III, such as IIIC. PAT059494-WO-PCT 9. Ribociclib succinate for use according to any one of embodiments 1 to 8, wherein the breast cancer is of the ductal subtype. 10. Ribociclib succinate for use according to any one of embodiments 1 to 9, wherein the patient is Asian. 11. Ribociclib succinate for use according to any one of embodiments 1 to 10, wherein the method is an adjuvant treatment because the patient has received at least one prior treatment for breast cancer selected from the group consisting of surgery, chemotherapy, endocrine therapy, and radiation therapy. 12. Ribociclib succinate for use according to embodiment 11, wherein the patient has not had a mastectomy. 13. Ribociclib succinate for use according to any one of embodiments 1 to 12, wherein the method improves overall survival (OS), distant disease-free survival (DDFS), and / or recurrence free survival (RFS) of the breast cancer in the patient for at least 36 months; or the method reduces the risk of recurrence of the breast cancer in the patient for at least 36 months. L. Additional exemplary embodiments Additional methods of treatment and uses of ribociclib are provided in the following embodiments. . A method of preventing recurrence of breast cancer in an adult patient who has received a prior treatment for HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, and (ii) a dose of an aromatase inhibitor, preferably letrozole or anastrozole. . A method of treating an adult patient in remission from HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, and (ii) a dose of an aromatase inhibitor, preferably letrozole or anastrozole. . A method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient in need thereof, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle and (ii) an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle. PAT059494-WO-PCT 4. The method of any one of embodiments 1 to 3, wherein the ribociclib is a pharmaceutically acceptable ribociclib salt. 5. The method of embodiment 4, wherein the ribociclib salt is ribociclib succinate. 6. The method of any one of embodiments 1, 2, 4, and 5, wherein dose of ribociclib is not 600 mg / day. 7. The method of any one of embodiments 1 to 5, wherein the dose of ribociclib is 200 mg / day or 400 mg / day. 8. The method of embodiment 7, wherein ribociclib is administered as ribociclib succinate, and the total dose of ribociclib is 200 mg / day. 9. The method of embodiment 7, wherein ribociclib is administered as ribociclib succinate, and the total dose of ribociclib is 400 mg / day. 10. The method of embodiment 7, wherein the ribociclib is administered at a dose of 400 mg / day for a period of time, after which a dose of 200 mg / day ribociclib is administered. 11. The method of any one of embodiments 1 to 10, wherein the dose of ribociclib is administered orally. 12. The method of any one of embodiments 1 to 11, wherein the dose of ribociclib is administered in tablet form. 13. The method of any one of embodiments 1 to 12, wherein the aromatase inhibitor is letrozole or anastrozole. 14. The method of any one of embodiments 1 to 13, wherein the aromatase inhibitor is administered orally. 15. The method of embodiment 13 or 14, wherein the letrozole is administered in a dose ranging from 1 mg / day to 4 mg / day. 16. The method of embodiment 15, wherein the letrozole is administered in a dose of 2.5 mg / day. 17. The method of embodiment 13 or 14, wherein the anastrozole is administered in a dose ranging from 0.5 mg / day to 1.5 mg / day. 18. The method of embodiment 17, wherein the anastrozole is administered in a dose of 1 mg / day. 19. A method of treating breast cancer recurrence in an adult patient who has received at least one prior treatment for HR+ / HER2- stage II or III early breast cancer and who has PAT059494-WO-PCT no detectable signs or symptoms of breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1 to 21 of a 28-day cycle, and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle. 20. A method of treating an adult patient who is in remission from HR+ / HER2- stage II or stage III early breast cancer and in need of adjuvant treatment, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1-21 of a 28-day cycle and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle. 21. The method of any one of embodiments 1 to 20, wherein the treatment comprises administering a gonadotropin-releasing hormone agonist. 22. The method of embodiment 21, wherein the gonadotropin-releasing hormone agonist is goserelin. 23. The method of embodiment 22, wherein the goserelin is administered in a dose ranging from 2 mg to 5 mg. 24. The method of embodiment 23, wherein the dose of goserelin is 3.6 mg. 25. The method of any one of embodiments 22 to 24, wherein the goserelin is administered subcutaneously. 26. The method of any one of embodiments 22 to 25, wherein the goserelin is administered once every 4 weeks. 27. The method of any one of embodiments 1 to 20, wherein the patient is a postmenopausal woman. 28. The method of any one of embodiments 1 to 26, wherein the patient is a premenopausal woman or a man. 29. The method of any one of embodiments 1 to 28, wherein the treatment is administered to the patient for at least 12 months. 30. The method of embodiment 29, wherein the treatment is administered to the patient for at least 24 months. 31. The method of embodiment 29 or embodiment 30, wherein the treatment is administered to the patient for at least 36 months. PAT059494-WO-PCT 32. The method of any one of embodiments 29 to 31, wherein the treatment is administered to the patient for at least 48 months. 33. The method of any one of embodiments 29 to 32, wherein the treatment is administered to the patient for at least 60 months. 34. The method of any one of embodiments 1 to 33, wherein the breast cancer is ER+ and PR+. 35. The method of any one of embodiments 1 to 33, wherein the breast cancer is ER- and PR+. 36. The method of any one of embodiments 1 to 33, wherein the breast cancer is ER+ and PR-. 37. The method of any one of embodiments 1 to 36, wherein the breast cancer has a histological subtype that is ductal. 38. The method of any one of embodiments 1 to 37, wherein the breast cancer has a histological subtype that is lobular. 39. The method of any one of embodiments 1 to 38, wherein the breast cancer is a stage IIA cancer or a stage IIB cancer. 40. The method of embodiment 39, wherein the breast cancer is a stage IIA cancer. 41. The method of embodiment 39, wherein the breast cancer is a stage IIB cancer. 42. The method of any one of embodiments 1 to 38, wherein the breast cancer is a stage IIIA cancer, a stage IIIB cancer, or a stage IIIC cancer. 43. The method of embodiment 42, wherein the breast cancer is a stage IIIA cancer. 44. The method of embodiment 42, wherein the breast cancer is a stage IIIB cancer. 45. The method of embodiment 42, wherein the breast cancer is a stage IIIC cancer. 46. The method of any one of embodiments 1 to 45, wherein the treatment is administered irrespective of the nodal status of the breast cancer. 47. The method of any one of embodiments 1 to 46, wherein the breast cancer has a nodal status selected from N0, N1, N2, and N3. 48. The method of embodiment 46 or 47, wherein the breast cancer has a nodal status of N0. PAT059494-WO-PCT 49. The method of embodiment 46 or 47, wherein the breast cancer has a nodal status of N1 to N3. 50. The method of embodiment 46 or 47, wherein the breast cancer has a nodal status of N1. 51. The method of embodiment 46 or 47, wherein the breast cancer has a nodal status of N2. 52. The method of embodiment 46 or 47, wherein the breast cancer has a nodal status of N3. 53. The method of any one of embodiments 1 to 52, wherein the breast cancer comprises one or more cells having a histological grade selected from G1, G2, or G3. 54. The method of embodiment 53, wherein the breast cancer comprises one or more cells having the histological grade G1. 55. The method of embodiment 53, wherein the breast cancer comprises one or more cells having the histological grade G2. 56. The method of embodiment 53, wherein the breast cancer comprises one or more cells having the histological grade G3. 57. The method of any one of embodiments 1 to 56, wherein the breast cancer comprises a tumor of category T0, T1, T2, T3, or T4. 58. The method of embodiment 57, wherein the breast cancer comprises a tumor of category T1, T2, or T3. 59. The method of embodiment 57, wherein the breast cancer comprises a tumor of category T0. 60. The method of embodiment 57 or 58, wherein the breast cancer comprises a tumor of category T1. 61. The method of embodiment 57 or 58, wherein the breast cancer comprises a tumor of category T2. 62. The method of embodiment 57 or 58, wherein the breast cancer comprises a tumor of category T3. 63. The method of embodiment 57, wherein the breast cancer comprises a tumor of category T4. PAT059494-WO-PCT 64. The method of any one of embodiments 1 to 63, wherein the breast cancer has a Ki67 status of 20 or lower. 65. The method of any one of embodiments 1 to 63, wherein the breast cancer has a Ki67 status of greater than 20. 66. The method of any one of embodiments 1 to 65, wherein prior to the administration, the patient has received a loading dose of (i) ribociclib and / or (ii) an endocrine therapy. 67. The method of any one of embodiments 1 to 18 and 20 to 66, wherein the patient has received at least one prior treatment for cancer. 68. The method of embodiment 19 or 67, wherein the prior treatment is an adjuvant treatment after another prior treatment. 69. The method of embodiment 67 or 68, wherein the prior treatment is surgery. 70. The method of embodiment 69, wherein the surgery comprises a complete surgical resection of the cancer. 71. The method of embodiment 69 or 70, wherein the surgery is a mastectomy. 72. The method of embodiment 67 or 68, wherein the prior treatment is a chemotherapy. 73. The method of embodiment 72, wherein the prior treatment is an adjuvant chemotherapy. 74. The method of embodiment 72, wherein the prior treatment is a neoadjuvant chemotherapy. 75. The method of embodiment 67 or 68, wherein the prior treatment is an endocrine therapy. 76. The method of embodiment 67 or 68, wherein the prior treatment is radiation therapy. 77. The method of any one of embodiments 19 and 67 to 76, wherein the patient did not respond to the prior treatment. 78. The method of any one of embodiments 1 to 77, wherein the patient is located in a geographic region selected from North America, Western Europe, or Oceania. 79. The method of any one of embodiments 1 to 78, wherein the patient is Asian. 80. The method of any one of embodiments 1 to 79, wherein the patient is 18 to 45 years of age. PAT059494-WO-PCT 81. The method of any one of embodiments 1 to 79, wherein the patient is 45 to 54 years of age. 82. The method of any one of embodiments 1 to 79, wherein the patient is 54 to 64 years of age. 83. The method of any one of embodiments 1 to 79, wherein the patient is greater than 64 years of age. 84. The method of any one of embodiments 1 to 83, wherein the patient has a BMI of 25 or higher. 85. The method of any one of embodiments 1 to 83, wherein the patient has a BMI lower than 25. 86. The method of any one of embodiments 1 to 85, wherein the treatment improves a condition of the patient relative to a patient not receiving the treatment and / or relative to the condition in the patient prior to treatment. 87. The method of any one of embodiments 1 to 86, wherein the treatment reduces the risk of invasive disease. 88. The method of embodiment 87, wherein the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than 1 when the risk is calculated relative to patients not receiving the treatment. 89. The method of embodiment 88, wherein the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.78 when the risk is calculated relative to patients not receiving the treatment. 90. The method of any one of embodiments 1 to 26 and 28 to 89, wherein the patient is a premenopausal woman or a man and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.72 when the risk is calculated relative to patients receiving the treatment. 91. The method of any one of embodiments 87 to 89, wherein the cancer is HR+ / HER2- stage III early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.74 when the risk is calculated relative to patients not receiving the treatment. 92. The method of any one of embodiments 87 to 89, wherein the cancer is HR+ / HER2- stage II early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.76 when the risk is calculated relative to patients not receiving the treatment. PAT059494-WO-PCT 93. The method of any one of embodiments 87 to 89, wherein the cancer is HR+ / HER2- stage III early breast cancer, and the treatment yields at least a 25% reduction in the risk of invasive disease corresponding to a hazard ratio of 0.75 when the risk is calculated relative to patients not receiving the treatment. 94. The method of any one of embodiments 1 to 93, wherein the treatment reduces the risk of invasive disease to a similar level for patient subgroups comprising patients with stage II early breast cancer, stage III early breast cancer, patients who are premenopausal women or men, and patients who are postmenopausal women. 95. The method of any one of embodiments 1 to 94, wherein the treatment yields no deterioration in overall survival corresponding to a hazard ratio of 0.76 when the risk is calculated relative to patients not receiving the treatment. 96. The method of any one of embodiments 1 to 95, wherein the treatment reduces and / or prevents one or more of recurrence of the cancer, spread of the cancer, development and / or growth of an additional cancer, and risk of death from the cancer. 97. The method of embodiment 96, wherein the treatment reduces the recurrence of cancer, wherein the recurrence is one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, and distant recurrence. 98. The method of embodiment 96, wherein the treatment reduces the spread of cancer, wherein the spread of cancer is an invasive contralateral breast cancer or an additional primary invasive cancer. 99. The method of any one of embodiments 1 to 98, wherein the treatment prevents death from cancer. XI. DEFINITIONS Other than in the examples, or where otherwise indicated, all numbers expressing quantities of ingredients, dosages or reaction conditions used herein should be understood as modified in all instances by the term “about” as that term would be interpreted by the person skilled in the relevant art. The term “about” as used herein is equivalent to ± 10% of a given numerical value, unless otherwise stated. “Adjuvant therapy” (or adjuvant treatment) refers to a treatment given after a primary treatment, e.g., in order to lower the risk that the disease will recur. In cancer, an adjuvant therapy may be administered, inter alia, to lower the risk of cancer recurrence, for example, by destroying cancer cells that remain after a primary treatment. For example, a treatment comprising a dose PAT059494-WO-PCT of ribociclib in combination with an aromatase inhibitor may be administered as an adjuvant after a primary treatment, e.g., comprising surgery, radiation therapy, and / or chemotherapy. “Neoadjuvant therapy” (or neoadjuvant treatment) refers to a treatment delivered before a primary treatment. In cancer, a neoadjuvant therapy may, inter alia, reduce the size of a tumor or kill cancer cells that have spread. "Co-administer," "co-administration," or "combined administration" or the like are meant to encompass administration of the selected therapeutic agents to a single patient, and encompass treatment regimens in which the agents are not necessarily administered by the same route of administration or at the same time. "Combination" refers to either a fixed combination of two or more agents (also referred to as co- agents or combination partners), e.g., in one dosage unit form, or a nonfixed combination (or kit of parts) for the combined administration where a first agent (also referred to as a first therapeutic agent) and a second agent (also referred to as a second therapeutic agent) may be administered independently at the same time or separately within time intervals, e.g., where these time intervals allow the combination partners to provide a cooperative, e.g. synergistic effect. The term "combined administration" or the like as utilized herein is meant to encompass administration of the selected combination partners to a single subject in need thereof (e.g. a patient), and is intended to include treatment regimens in which the agents are not necessarily administered by the same route of administration or at the same time. The term "fixed combination" means that the active ingredients, e.g. combination partners, are both administered to a patient simultaneously in the form of a single dosage. The terms "non-fixed combination" or "kit of parts" mean that the active ingredients, e.g. combination partners, are provided separately, e.g., within a kit, and / or are both administered to a patient as separate dosage forms either concurrently or sequentially with no specific time limits, wherein such administration provides therapeutically effective levels of the two compounds in the body of the patient. "Dose range" refers to an upper and a lower limit of an acceptable variation of the amount of therapeutic agent specified. Typically, a dose of the agent in any amount within the specified range can be administered to patients undergoing treatment. A “loading dose” may be an initial dose of a drug that may be given at or prior to the beginning of a course of treatment before dropping down to a different, typically lower dose (e.g., a treatment or maintenance dose). A loading dose may be a single dose or short duration regimen of a compound which is administered to the subject to rapidly increase the blood concentration level of the drug. Suitably, a short duration regimen for use herein will be from: 1 to 14 days; e.g., from 1 to 7 days; e.g., from 1 to 3 days; e.g., for three days; e.g., for two days; e.g., for one PAT059494-WO-PCT day. In some embodiments, the “loading dose” can increase the blood concentration of the drug to a therapeutically effective level. In some embodiments, the “loading dose” can increase the blood concentration of the drug to a therapeutically effective level in conjunction with a treatment dose of the drug. The “loading dose” can be administered once per day, or more than once per day (e.g., up to 4 times per day). In some embodiments, a loading dosage may be used for drug molecules that have a long half-life or slow elimination in vivo. "Pharmaceutical preparation" or "pharmaceutical composition" refers to a mixture or solution containing at least one therapeutic agent suitable to be administered to a warm-blooded animal, e.g., a human. "Pharmaceutically acceptable" refers to those compounds, materials, compositions and / or dosage forms, which are, within the scope of sound medical judgment, suitable for contact with the tissues of mammals, especially humans, without excessive toxicity, irritation, allergic response and other problem complications commensurate with a reasonable benefit / risk ratio. "Subject," "patient," or "warm-blooded animal" is intended to include animals. Examples of subjects include mammals, e.g., humans, dogs, cows, horses, pigs, sheep, goats, cats, mice, rabbits, rats, and transgenic non-human animals. In certain embodiments, the subject is a human. "Therapeutically effective" preferably relates to an amount of a therapeutic agent that is capable of providing a therapeutic response in a subject or prophylactically effective against the progression of a cancer. A therapeutically effective treatment or amount of treatment need not completely treat a subject, but may partially or completely delay, ameliorate, reverse, or reduce at least one or more signs, symptoms, or manifestations of a disease. "Treatment" or “treating” can be prophylactic and / or therapeutic (including but not limited to palliative, symptom-alleviating, symptom-reducing) as well as the delay of progression of a disease or disorder such as cancer. The term "prophylactic" means the prevention or delay of the onset or recurrence of a disease such as cancer. The term "delay of progression" as used herein means administration of the combination to patients being in a pre-stage or in an early phase of the cancer to be treated, a pre-form of the corresponding cancer is diagnosed and / or in a patient diagnosed with a condition under which it is likely that a corresponding cancer will develop. “Tumor” refers to an abnormal mass of tissue. Tumors may comprise cancer cells. Tumors may be described as benign if they do not spread into or invade nearby tissues or other parts of the body. Tumors may be described as malignant if they spread into other tissues or parts of the body. PAT059494-WO-PCT

[0002] XII. ABBREVIATIONS AE Adverse Event AI Aromatase Inhibitor AJCC American Joint Committee on Cancer ALND Axillary Lymph Node Dissection ALP Alkaline Phosphatases ALT Alanine Transaminase ANC Absolute Neutrophil Count aPTT Activated Partial Thromboplastin Time AST Aspartate Transaminase ATC Anatomical Therapeutic Chemical AUC Area Under the Curve AV Atrioventricular BC Breast Cancer BCRP Breast Cancer Resistance Protein BSEP Bile Salt Export Pump CA Competent Authority CBP Childbearing Potential CCND1 Cyclin D1 CDK Cyclin-Dependent Serine-Threonine Protein Kinases CI Confidence Interval CISH Chromogenic In Situ Hybridization Ctrough Trough concentration Cmax Maximum Serum Concentration CMO&PS Chief Medical Office and Patient Safety COSMIC Catalogue of Somatic Mutations in Cancer CRF Case Report Form; the term CRF can be applied to either EDC or Paper CSR Clinical Study Report CT Computed Tomography CTCAE Common Terminology Criteria for Adverse Events ctDNA Circulating Tumor DNA ctRNA Circulating Tumor RNA CV Coefficient of Variation CYP Cytochrome P450 DCIS Ductal Carcinoma in situ PAT059494-WO-PCT DDFS Distant Disease Free Survival DDI Drug-Drug Interaction DHEA Dehydroepiandrosterone DILI Drug-Induced Liver Injury DNA Deoxyribonucleic Acid DX Diagnosis EBC Early Breast Cancer EBCTCG EBC Trialists’ Collaborative Group ECG Electrocardiogram ECHO Echocardiogram ECOG Eastern Cooperative Oncology Group EDC Electronic Data Capture eGFR Estimated Glomerular Filtration Rate EORTC-QLQ European Organization for Research and Treatment of Cancer’s Core Quality of Life Questionnaire EOT End of Treatment EQ-SD-SL EuroQoL 5-Level Instrument ER Estrogen Receptor ET Endocrine Therapy FAS Full Analysis Set FDA Food and Drug Administration FDG-PET Fludeoxyglucose Positron Emission Tomography FISH Fluorescence In Situ Hybridization FSH Follicle-stimulating hormone G2-3 Histologic Grade 2-3 GCP Good Clinical Practice GDPR General Data Protection Regulation (EU) 2016 / 679 GGT Gamma-glutamyl Transferase GI Gastrointestinal GnRH Gonadotropin-releasing Hormone GWAS Genome-Wide Association Studies HADS Hospital Anxiety and Depression Scale HBV Hepatitis B virus β-hCG Beta Human Chorionic Gonadotropin HCV Hepatitis C Virus HER2 Human Epidermal Growth Factor Receptor 2 HIPAA Health Insurance Portability and Accountability Act (US) PAT059494-WO-PCT HIV Human Immunodeficiency Virus HLA Human Leukocyte Antigen HR Hormone Receptor IB Investigator’s Brochure IBTR Invasive ipsilateral breast tumor ICH International Council for Harmonization iDFS Invasive Disease-Free Survival IDMC Independent Data Monitoring Committee IEC Independent Ethics Committee IHC Immunohistochemistry ILD Interstitial Lung Disease IMP Investigational Medicinal Product IN Investigator Notification INR International Normalized Ratio IRB Institutional Review Board IRT Interactive Response Technology IUD Intrauterine Device i.v. Intravenous(ly) LC-MS / MS Liquid Chromatography-tandem Mass Spectrometry LDH Lactate Dehydrogenase LFT Liver Function Test LLOQ Lower Limit of Quantification LPLV Last Patient Last Visit LRRFS Loco-regional Recurrence-Free Survival LVEF Left Ventricular Ejection Fraction MATE1 Multidrug and Toxin Extrusion Protein-1 MDRD Modification of Diet in Renal Disease MI Myocardial Infarction MRI Magnetic Resonance Imaging msec Milliseconds MUGA Multiple Gated Acquisition NaF-PET Sodium Fluoride Positron Emission Tomography NCI National Cancer Institute NSAI Non-Steroidal Aromatase Inhibitor OCT2 Organic Cation Transporter 2 ORR Overall Response Rate OS Overall survival PAT059494-WO-PCT PAS Pharmacokinetics Analysis Set PFS Progression-Free Survival P-gp P-glycoprotein PgR or PR Progesterone Receptor PICF Patient Informed Consent Form PK Pharmacokinetics PK-ANC PK-Absolute Neutrophil Count PK-QTcF PK-QT Interval in the ECG corrected according to the formula of Fridericia PPS Per-Protocol Set PRO Patient Reported Outcomes PT Prothrombin Time QD Once a day QoL Quality of Life QT QT Interval in the ECG QTc QT Interval in the ECG (corrected) QTcF QT Interval in the ECG (corrected according to the formula of Fridericia) Rb Retinoblastoma RFS Recurrence-Free Survival RNA Ribonucleic Acid RoW Rest of the World SAE Serious Adverse Event SAP Statistical Analysis Plan SC Steering Committee SEER Surveillance, Epidemiology, and End Results SERM Selective estrogen receptor modulators SGOT Serum Glutamic Oxaloacetic Transaminase SGPT Serum Glutamic Pyruvic Transaminase SISH Silver in Situ Hybridization SLN Sentinel Lymph Node STEEP Standardized Definitions for Efficacy End Points (in Adjuvant Breast Cancer Trials) SUSAR Suspected Unexpected Serious Adverse Reaction T1 / 2Half-life TBIL Total Bilirubin TdP Torsades de Pointes TEAE Treatment-emergent adverse effects TEN Toxic Epidermal Necrolysis PAT059494-WO-PCT TmaxThe time at which the maximum observed concentration (Cmax) occurs TNM Tumor, Node and Metastasis ULN Upper Limit of Normal US Ultrasound TRIO Translational Research in Oncology VAS Visual Analogue Scale WBC White Blood Cell WHO World Health Organization XIII. REFERENCES All publications, patents and patent applications referred to herein are incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference in its entirety. XIV. EXAMPLES Hereinafter, the present invention is described in more detail and specifically with reference to the examples, which however are not intended to limit the present invention. a. Example 1. CLINICAL TRIAL OVERVIEW The clinical phase 3 trial with the protocol title “A phase III, multicenter, randomized, open-label trial to evaluate efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, early breast cancer” is described at ClinicalTrials.gov with the Identifier: NCT03701334 (the entire disclosure of that webpage is incorporated herein by reference). The trial has been and is being performed according to the protocol described below. Study design: See FIG.1. Synopsis of the clinical protocol for the NATALEE trial (New Adjuvant TriAl with Ribociclib [LEE011]) Protocol Title A phase III, multicenter, randomized, open-label trial to evaluate efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, early breast cancer (New Adjuvant TriAl with Ribociclib [LEE011]: NATALEE). Trial Number CLEE011O12301C (TRIO033) Trial Sponsor Novartis PAT059494-WO-PCT Participating Approximately 425 sites worldwide will participate in the trial. Sites Investigational Ribociclib (LEE011) Drug Indication Adjuvant treatment of hormone receptor (HR)-positive, HER2-negative, early breast cancer (EBC). Population Pre and postmenopausal women and men with HR-positive, HER2- negative EBC, after adequate surgical resection, who are eligible for adjuvant non-steroidal aromatase inhibitor (NSAI) for at least 5 years. Objectives / Objective Endpoint Endpoints Primary To compare iDFS for ribociclib + ET iDFS using STEEP criteria versus ET in patients with HR- (Standardized Definitions for positive, HER2-negative, EBC Efficacy End Points in Adjuvant Breast Cancer Trials), as assessed by Investigator Secondary 1. To evaluate the two treatment RFS using STEEP criteria arms with respect to recurrence-free survival (RFS) 2. To evaluate the two treatment DDFS using STEEP criteria arms with respect to distant disease- free survival (DDFS) 3. To evaluate the two treatment OS arms with respect to overall survival (OS) 4. To evaluate patient reported Change from baseline in the outcomes (PRO) for health-related physical functioning sub-scale quality of life (QoL) in the two score and global health status / QoL treatment arms scale score as assessed by EORTC QLQ-C30 5. To evaluate safety and tolerability Frequency and severity of adverse of the treatment regimen events (AEs), laboratory and PAT059494-WO-PCT electrocardiogram (ECG) abnormalities 6. To characterize the PK parameters such as Ctrough and pharmacokinetics (PK) of ribociclib other applicable parameters for when given in combination with NSAI ribociclib (and goserelin if applicable) Trial Design This is a phase III, multicenter, randomized, open-label trial to evaluate and Treatment the efficacy and safety of ribociclib with ET as an adjuvant treatment in women and men with HR-positive, HER2-negative EBC. iDFS is the primary endpoint of the trial, as defined per the STEEP System. The trial will include pre and postmenopausal women and men with HR- positive, HER2-negative EBC, with an Anatomic Stage Group III, IIB or a subset of Stage IIA cases (as defined in Inclusion Criterion #8, see below), after adequate surgical resection, radiotherapy (if indicated), adjuvant or neoadjuvant chemotherapy (if indicated), and who are deemed to be eligible for adjuvant ET for at least 60 months of duration. See FIG.1. Approximately 5,000 patients will be randomized (using an Interactive Response Technology system [IRT]) into two treatment arms in a 1:1 ratio to: • Investigational arm: • Ribociclib 400 mg by mouth once daily on days 1 to 21 of a 28-day cycle, for 36 months since randomization (approximately 39 cycles). And • ET consisting of: • For postmenopausal women: letrozole 2.5 mg by mouth once daily continuously or anastrozole 1 mg by mouth once daily continuously. PAT059494-WO-PCT • For premenopausal women and men: letrozole 2.5 mg by mouth once daily continuously or anastrozole 1 mg by mouth once daily continuously, combined with goserelin 3.6 mg subcutaneously once every 4 weeks. Duration of ET in the trial will be 60 months from the randomization date. • Control arm: • ET: Same as in the Investigational arm. In both arms, ET will be administered according to the local clinical guidelines and current local prescribing information. Subsequent ET (or any other anti-cancer treatment) given after the protocol-required 60 months of ET (or after premature discontinuation of ET in the trial) will be administered according to the Investigator’s clinical judgment and is not considered a trial treatment. Randomization will be stratified by the following factors: • Menopausal status: premenopausal women and men vs. postmenopausal women • AJCC 8thedition Anatomic Stage Group: Anatomic Stage Group II vs. Anatomic Stage Group III • Prior neoadjuvant / adjuvant chemotherapy: yes vs. no • Geographical region: North America / Western Europe / Oceania vs. rest of the world Enrollment of patients with Anatomic Stage Group II is capped at approximately 2,000 patients. The trial will include screening, treatment, and follow up phases. The trial includes an exploratory component that requires collection of tumor and blood samples (except for patients enrolled in China). Eligibility Inclusion Criteria Criteria Patients eligible for inclusion in this trial must meet all of the following criteria: PAT059494-WO-PCT Signed and dated Patient Informed Consent Form (PICF) obtained prior to any trial-specific screening procedure. Patient is ≥ 18 years-old at the time of PICF signature. Patient is female with known menopausal status at the time of randomization or initiation of adjuvant ET (whichever occurs earlier), or male. Postmenopausal status is defined as: • Patient underwent bilateral oophorectomy, or • Age ≥ 60 years, or • Age < 60 years and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression) and Follicle-stimulating hormone (FSH) and plasma estradiol are in the postmenopausal ranges per local normal ranges. • If taking tamoxifen or toremifene and age <60 years, then FSH and plasma estradiol level in postmenopausal ranges. Notes • In women who are premenopausal at the beginning of adjuvant chemotherapy, amenorrhea is not a reliable indicator of menopausal status as ovarian function may still be intact or resume despite anovulation / amenorrhea. For these women with therapy-induced amenorrhea, serial measurements of FSH and / or estradiol per local clinical guidelines are required for determination of postmenopausal status. • All women who do not meet the criteria for postmenopausal status are considered premenopausal for the purpose of this trial. Patient with histologically confirmed unilateral primary invasive adenocarcinoma of the breast with a date of initial cytologic or histologic diagnosis (i.e. date of the pathology report that confirmed the BC diagnosis) within 18 months prior to randomization. Patient PAT059494-WO-PCT with a multicentric and / or multifocal tumor is eligible if all histopathologically examined lesions meet the pathologic criteria in inclusion criteria 5 and 6. Patient has breast cancer that is positive for ER and / or PgR according to the local laboratory as determined on the most recently analyzed tissue sample. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory). Patient (except those enrolled in China) has available archival tumor tissue from the surgical specimen, for submission to a central laboratory (Note: in patients that underwent neoadjuvant systemic therapy and had a pathologic complete response, archival tumor tissue at the time of the initial diagnosis or before the administration of neoadjuvant therapy is mandatory). Patient, after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and belongs to one of the following categories: • Anatomic Stage Group III, or • Anatomic Stage Group IIB, or • Anatomic Stage Group IIA that is either: • N1, or • N0, with: • Grade 3, or • Grade 2, with any of the following criteria: • Ki67 ≥ 20%, or • Oncotype DX Breast Recurrence Score ≥ 26, or • Prosigna / PAM50 categorized as high risk, or PAT059494-WO-PCT • MammaPrint categorized as high risk, or • EndoPredict EPclin Risk Score categorized as high risk Notes: • For patients whose tumors are Anatomic Stage IIA, N0: • If Grade is 1 or unknown (Gx), patient is not eligible. • If Grade 2, the gene expression test results (by Oncotype DX, Prosigna / PAM50, MammaPrint or EndoPredict EPclin) or Ki67 levels should be used if obtained as per local practice (i.e. are not mandatory for the purpose of the trial). Results must be available at screening. • Patients that received neoadjuvant treatment must meet the above criteria (for stage, and if Stage IIA, N0, also for grade and Ki67 or gene expression test) in any presurgical staging / sample and / or in the surgical specimen. • Categorization into the AJCC 8thedition Anatomic Stage Groups requires determination of the T, N and M categories. ALND is the preferred method for axillary lymph node staging, however SLN dissection can be used to determine the N category in the following cases: • No metastasis in SLN (patient is considered as pN0). • Only micrometastasis in SLN (patient is considered as pN1mi). • Patients with T1-2 and no clinically-evident nodes prior to surgery, no neoadjuvant chemotherapy, at least one macrometastasis in 1 or 2 SLNs, no matted nodes or gross extranodal disease at the time of SLN dissection (patient is considered as pN1). In all other cases, ALND is required to determine the N category. PAT059494-WO-PCT If indicated, patient has completed adjuvant and / or neoadjuvant chemotherapy according to the institutional guidelines, prior to screening. If indicated, patient has completed adjuvant radiotherapy according to the institutional guidelines, prior to screening. Patient has no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for 5 years (since randomization date) or more. Patient may have already received any standard neoadjuvant and / or adjuvant ET at the time of PICF signature, but randomization should occur within 12 months of the initial start date of ET. Ovarian suppression or short term ET for fertility preservation is not considered neoadjuvant / adjuvant ET. If patient was receiving tamoxifen or toremifene as adjuvant ET, a washout period of 5 half-lives (i.e. 35 days) prior to randomization is required (during that period patient can take AI). Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Patient has adequate bone marrow and organ function as defined by the following local laboratory values: • Absolute neutrophil count (ANC) ≥ 1.5 × 109 / L • Platelets ≥ 100 × 109 / L • Hemoglobin ≥ 9.0 g / dL • Estimated glomerular filtration rate (eGFR) ≥ 30 mL / min / 1.73m2according to the Modification of Diet in Renal Disease (MDRD) formula • Alanine transaminase (ALT) < 2.5 × Upper Limit Normal (ULN) • Aspartate transaminase (AST) < 2.5 × ULN • Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN in patients with well documented Gilbert’s Syndrome PAT059494-WO-PCT • International normalized ratio (INR) ≤ 1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to randomization) • Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements (the local laboratory value should be documented within normal limits after the correction) before randomization: • Potassium • Magnesium • Total Calcium (corrected for serum albumin) Standard 12-lead ECG values assessed by a central laboratory, as: • QTcF interval (QT interval using Fridericia’s correction) at screening < 450 milliseconds (msec) • Resting heart rate 50-90 beats per minute (determined from the ECG) Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures. Women of childbearing potential (CBP), defined as all women physiologically capable of becoming pregnant (see Inclusion Criterion #18 for additional information), must have confirmed negative serum pregnancy test (for β-hCG) within 14 days prior to randomization. Women of CBP must be willing to use highly effective methods of contraception. Contraception must continue during the trial treatment and for 21 days after stopping the treatment. Highly effective contraception methods include: • Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. PAT059494-WO-PCT • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking trial treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. • Male partner sterilization (at least 6 months prior to randomization). For female patients on the trial the vasectomized male partner should be the sole partner for that patient. If vasectomy of the male partner is the highly effective method of contraception chosen, the success of the vasectomy should be medically confirmed according to local practice. • Placement of an intrauterine device (IUD). Notes: • Use of oral (estrogen and progesterone), transdermal, injected, implanted, hormone containing intrauterine system or any other hormonal method of contraception is not allowed in this trial. • Women are considered of CBP unless: they have had ≥ 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment she is considered not of CBP. • After the end of trial treatment, patients should use effective contraception according to local guidelines. Exclusion Criteria Patients eligible for this trial must not meet any of the following criteria: PAT059494-WO-PCT atient has received any CDK4 / 6 inhibitor. atient has received prior treatment with tamoxifen, raloxifene or AIs for reduction in risk (“chemoprevention”) of breast cancer and / or treatment for osteoporosis within the last 2 years prior to randomization. Patient is concurrently using hormone replacement therapy. atient has received prior treatment with anthracyclines at cumulative doses of 450 mg / m² or more for doxorubicin, or 900 mg / m² or more for epirubicin. atient with a known hypersensitivity to any of the excipients of ribociclib and / or ET (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy allergy). atient with distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8thedition) and / or evidence of recurrence after curative surgery. atient is concurrently using other anti-neoplastic therapy with the exception of adjuvant ET (see Inclusion Criterion #12). atient has had major surgery, chemotherapy or radiotherapy within 14 days prior to randomization. atient has not recovered from clinical and laboratory acute toxicities related to prior anti-cancer therapies to a NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.03 Grade ≤1 at day of randomization. Exceptions to this criterion: patients with any grade of alopecia, amenorrhea, grade 2 neuropathy are allowed to enter the trial or other toxicities not considered a safety risk for the patient as per Investigator’s discretion, are allowed to enter the trial. atient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before randomization. Note: Patients with adequately treated, basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ are eligible. PAT059494-WO-PCT atient has known history of human immunodeficiency virus (HIV) infection (testing is not mandatory, unless required by local regulation). atient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (testing is not mandatory, unless required by local regulation). linically significant, uncontrolled heart disease and / or cardiac repolarization abnormality, including any of the following: • History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft within 6 months prior to trial entry. • Documented cardiomyopathy. • Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) (testing not mandatory) • Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: • Risk factors for Torsades de Pointes (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant / symptomatic bradycardia. • Concomitant medication(s) with a known risk to prolong the QT interval and / or known to cause TdP that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting trial treatment). • Inability to determine the QTcF interval. • Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade Atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third degree AV block). PAT059494-WO-PCT • Uncontrolled arterial hypertension with systolic blood pressure > 160 mmHg. atient is currently receiving any of the following substances within 7 days before randomization: • Concomitant medications, herbal supplements, and / or fruits (e.g. grapefruit, pummellos, starfruit, Seville oranges) and their juices that are known as strong inhibitors or inducers of CYP3A4 / 5 • Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4 / 5 atient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting trial treatment, or has not fully recovered from side effects of such treatment. Note: The following uses of corticosteroids are permitted: a short duration (<5 days) of systemic corticosteroids; any duration of topical applications (e.g. for rash), inhaled sprays (e.g. for obstructive airways diseases), eye drops or local injections (e.g. intra-articular). atient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the oral trial treatments (e.g. uncontrolled ulcerative diseases, uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, or small bowel resection). atient has any other concurrent severe and / or uncontrolled medical condition that would, in the Investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other significant liver disease, active untreated or uncontrolled fungal, bacterial or viral infections, active infection requiring systemic anti- bacterial therapy, etc.) or limit life expectancy to ≤5 years. articipation in other studies involving investigational drug(s) within 30 days prior to randomization or within 5 half-lives of the investigational drug(s) (whichever is longer), or participation in any other type of medical research judged not to be scientifically or medically compatible with this trial. If the patient is enrolled or planned to be PAT059494-WO-PCT enrolled in another study that does not involve an investigational drug, the agreement of the Medical Monitor is required to establish eligibility. 19. Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial. Assessments Trial visits will occur at screening, randomization, during treatment, approximately 30 days after discontinuation of ribociclib (Investigational arm only), End of Treatment (EOT), approximately 30 days after discontinuation of all trial treatments and during Follow-up. Efficacy assessments Efficacy assessment for the primary endpoint of iDFS will include detection of locoregional relapse, distant relapse, ipsilateral and contralateral invasive BC, second primary invasive non-BCs and deaths. Assessments for events of recurrence will be done clinically every 12 weeks (± 2 weeks) for the first 24 months from randomization and every 24 weeks (± 3 weeks) thereafter. Mammography will be done annually. Recurrences suspected clinically will be confirmed by additional imaging and every effort should be done to also confirm them histologically / cytologically (unless unsafe per Investigator’s discretion). Survival status will be assessed up to 60 months after the last patient has been randomized, until death, withdrawal of consent, loss to follow- up or end of trial, whichever is earliest. Survival information can be obtained by clinical visits, telephone calls, or other means. Safety assessments Safety will be assessed for each patient and will include routine safety monitoring (AEs collection, laboratory testing of hematology, serum chemistry, measurement of vital signs, performance status, physical examination, and ECG). Assessments of QoL and healthcare resources utilization QoL will be evaluated by periodic questionnaires (i.e. EORTC QLQ-C30, EORTC QLQ-BR23, EQ-5D-5L and HADS), at screening and during the Treatment and Follow up Phases. PAT059494-WO-PCT Use of subsequent anti-cancer therapy, time to first subsequent anti- cancer therapy and healthcare resources utilization will be evaluated for each arm. PK assessments Approximately 130 patients from the Investigational arm will be part of the PK subset. Plasma samples for ribociclib determination will be obtained pre- and post-dose on C1D15. Statistical The primary efficacy analysis will be the comparison of the distribution of Methods iDFS between the two treatment arms using a stratified log-rank test at one-sided 2.5% level of significance, using strata information at the time of randomization. Distribution of iDFS will be estimated using the Kaplan- Meier method. The iDFS at the end of each year along with 95% confidence intervals will be presented for each of the two treatment arms. The stratified Cox regression will be used to estimate the hazard ratio of iDFS, along with 95% confidence interval, using strata information as per IRT at the time of randomization. RESULTS Overview of results Results from an interim analysis of the NATALEE trial: Kisqali plus endocrine therapy (ET) significantly reduced the risk of disease recurrence compared to standard ET alone in the adjuvant setting. NATALEE is the first and only positive Phase III study of a CDK4 / 6 inhibitor demonstrating consistent benefit in a broad population of patients with stage II and III HR+ / HER2- early breast cancer (EBC) at risk of recurrence, including those with no nodal involvement. The primary endpoint of invasive disease-free survival (iDFS) has been met. Kisqali plus ET significantly reduced the risk of disease recurrence, compared to standard adjuvant ET alone, with consistent benefit in patients with stage II and stage III EBC regardless of nodal involvement. • Study met its Primary Endpoint of iDFS at Interim Analysis 3 (426 / 500 events) • 1-sided p-value of 0.0014 met the early efficacy stopping boundary (p < 0.0128) • Approx 25% reduction in the risk of iDFS (HR : 0.748 , 95% CI (0.619-0.906)) PAT059494-WO-PCT • 3y iDFS rate : RIB+ET : 90.4% vs ET alone : 87.1% ; Δ : 3.3% • Overall Consistent iDFS effect in key subgroups • Stage III – HR : 0.74 (0.59-0.92); Stage II – HR : 0.76 (0.52 – 1.1) • Premenopausal & Men – HR 0.72 (0.53 – 0.98); Postmenopausal – HR : 0.78 (0.613 – 0.997) • Positive trend seen for all 2ry efficacy endpoints : RFS, DDFS & OS • Any deterioration in overall survival (OS) can be ruled out : HR 0.76 (0.54 - 1.07), p-value : 0.0559 In terms of safety, the trial demonstrated a well-tolerated safety profile. Furthermore, the 400mg ribociclib dose demonstrated an improved profile with less overall toxicity, particularly dose- dependent adverse events (cardiac QT interval & neutropenia). There were no new safety findings compared to the known and established safety profile of ribociclib therapy. Discontinuation rates due to adverse events over a 3 year period were similar in early breast cancer patients as in metastatic breast cancer. Compared to the earlier ‘monarch-E’ trial, diarrhea was not a frequent (>5%) grade 3 or 4 adverse reaction, and no patients discontinued or reduced their ribociclib dose for this reason. In summary, patients in the RIB+ET arm demonstrated a significantly longer iDFS than ET alone (HR 0.748, p=0.0014), with 3 year iDFS rates increasing to 90.4% (vs.87.1%). The iDFS benefit was consistent across stratification factors and other subgroups. Secondary endpoints of overall survival, recurrence-free survival, and distant disease-free survival were consistently in favor of the RIB+ET arm. Moreover, addition of RIB had a favorable safety profile with no new signals. Overall, addition of RIB to the standard-of-care ET demonstrated a statistically significant and clinically meaningful improvement in iDFS, with a well-tolerated safety profile. The combined therapy can therefore be seen as suitable for use in a broad population of patients who have stage II or stage III HR+ / HRE2- early breast cancer, including N0 patients whose cancer has not spread to nearby lymph nodes. This is unexpected based on the results of other parallel studies. Assessment of Health-Related Quality of Life (HRQOL) in NATALEE QoL was analyzed after a median follow-up of 34 months. About 20% of patients had completed 3 years of ribociclib plus endocrine therapy. The prespecified analysis of HRQOL was based on patient-reported outcomes based on a number of survey instruments: the EORTC QLQ-C30 (European Organisation for Research and PAT059494-WO-PCT Treatment of Cancer Quality-of-Life questionnaire) for function (physical, social, and emotional) and global health status; EORTC QLQ-BR23 for breast cancer symptoms; the EQ-VAS (Euro- QoL visual analog scale) of the EQ-5D-5L; and the Hamilton Anxiety and Depression Scale (See also FIGS.5-8 for exemplary questionaires). The HRQOL of patients with HR+ / HER2− EBC was maintained with the addition of ribociclib to standard-of-care adjuvant NSAI vs NSAI alone. Physical functioning and Global Health scores were maintained over time in both the ribociclib + NSAI and NSAI alone arms. XV. Example 2. Trial Protocol The NATALEE trial has been and is being performed according to the protocol described in Appendix A. XVI. Example 3. First Interpretable Results and Updated Analysis First interpretable results are described in Appendix B. With 5.6 months of additional follow-up (median follow-up of 33.3 months) and 78.3% of patients having completed Kisqali® (ribociclib) investigational treatment, the updated analysis shows sustained iDFS benefit and stability in secondary endpoints including overall survival (OS). iDFS benefit remains consistent across key patient subgroups; among patients with stage II and stage III tumors, Kisqali lowered risk by 30% and 24.5%, respectively. Results reinforce the benefit seen at the earlier interim analysis, with a 25.1% (HR=0.749; 95% CI: 0.628, 0.892; p=0.0006) reduction in risk of disease recurrence in patients with stage II and III hormone receptor-positive / human epidermal growth factor receptor 2- negative (HR+ / HER2-) early breast cancer (EBC) treated with adjuvant Kisqali plus a non- steroidal aromatase inhibitor as standard endocrine therapy (ET) compared to ET alone. Kisqali iDFS benefit across pre-specified subgroups: PAT059494-WO-PCT Kisqali data across all secondary efficacy endpoints was also consistent, including distant disease-free survival (DDFS) (25.1% risk reduction) and recurrence-free survival (RFS) (27.3% risk reduction). With fewer than 4% of events in both treatment arms (3.3% in the Kisqali-ET arm and 3.4% in the ET only arm), overall survival (OS) results will continue to evolve in the longer term. The safety profile of Kisqali at the 400 mg dose remained consistent with previously reported results, with generally low-grade adverse events (AEs), other than laboratory abnormalities. AEs of special interest (grade 3 or higher) were neutropenia (44.3%), liver-related AEs (e.g., elevated transaminases) (8.6%), and QT interval prolongation (1.0%)1,2. No new safety signals were identified.XVII. Appendix A - Clinical Trial Protocol

[0003] PAT059494-WO-PCT

[0004] Approximately 425 sites will participate in the trial globally. The list of Investigators participating in the trial will be maintained by Translational Research in Oncology (TRIO). List of Abbreviations AE Adverse Event AI Aromatase Inhibitor AJCC American Joint Committee on Cancer ALND Axillary Lymph Node Dissection ALP Alkaline Phosphatases ALT Alanine Transaminase ANC Absolute Neutrophil Count aPTT Activated Partial Thromboplastin Time AST Aspartate Transaminase ATC Anatomical Therapeutic Chemical AUC Area Under the Curve AV Atrioventricular BC Breast Cancer BCRP Breast Cancer Resistance Protein BSEP Bile Salt Export Pump CA Competent Authority CBP Childbearing Potential CCND1 Cyclin D1 CDK Cyclin-Dependent Serine-Threonine Protein Kinases CI Confidence Interval CISH Chromogenic In Situ Hybridization Ctrough Trough concentration Cmax Maximum Serum Concentration CMO&PS Chief Medical Office and Patient Safety COSMIC Catalogue of Somatic Mutations in Cancer CRF Case Report Form; the term CRF can be applied to either EDC or Paper CSR Clinical Study Report CT Computed Tomography CTCAE Common Terminology Criteria for Adverse Events ctDNA Circulating Tumor DNA ctRNA Circulating Tumor RNA CV Coefficient of Variation CYP Cytochrome P450 DDFS Distant Disease Free Survival DDI Drug-Drug Interaction DHEA Dehydroepiandrosterone DILI Drug-Induced Liver Injury DNA Deoxyribonucleic Acid EBC Early Breast Cancer EBCTCG EBC Trialists’ Collaborative Group ECG Electrocardiogram ECHO Echocardiogram ECOG Eastern Cooperative Oncology Group EDC Electronic Data Capture PAT059494-WO-PCT eGFR Estimated Glomerular Filtration Rate EORTC-QLQ European Organization for Research and Treatment of Cancer’s Core Quality of Life Questionnaire EOT End of Treatment EQ-SD-SL EuroQoL 5-Level Instrument ER Estrogen Receptor ET Endocrine Therapy FAS Full Analysis Set FDA Food and Drug Administration FDG-PET Fludeoxyglucose Positron Emission Tomography FISH Fluorescence In Situ Hybridization FSH Follicle-stimulating hormone G2-3 Histologic Grade 2-3 GCP Good Clinical Practice GDPR General Data Protection Regulation (EU) 2016 / 679 GGT Gamma-glutamyl Transferase GI Gastrointestinal GnRH Gonadotropin-releasing Hormone GWAS Genome-Wide Association Studies HADS Hospital Anxiety and Depression Scale HBV Hepatitis B virusβ-hCGBeta Human Chorionic GonadotropinHCV Hepatitis C Virus HER2 Human Epidermal Growth Factor Receptor 2 HIPAA Health Insurance Portability and Accountability Act (US) HIV Human Immunodeficiency Virus HLA Human Leukocyte Antigen HR Hormone Receptor IB Investigator’s Brochure ICH International Council for Harmonization iDFS Invasive Disease-Free Survival IDMC Independent Data Monitoring Committee IEC Independent Ethics Committee IHC Immunohistochemistry ILD Interstitial Lung Disease IMP Investigational Medicinal Product IN Investigator Notification INR International Normalized Ratio IRB Institutional Review Board IRT Interactive Response Technology IUD Intrauterine Device i.v. Intravenous(ly) LC-MS / MS Liquid Chromatography-tandem Mass Spectrometry LDH Lactate Dehydrogenase LFT Liver Function Test LLOQ Lower Limit of Quantification LPLV Last Patient Last Visit LRRFS Loco-regional Recurrence-Free Survival LVEF Left Ventricular Ejection Fraction MATE1 Multidrug and Toxin Extrusion Protein-1 MDRD Modification of Diet in Renal Disease MI Myocardial Infarction PAT059494-WO-PCT MRI Magnetic Resonance Imaging msec Milliseconds MUGA Multiple Gated Acquisition NaF-PET Sodium Fluoride Positron Emission Tomography NCI National Cancer Institute NSAI Non-Steroidal Aromatase Inhibitor OCT2 Organic Cation Transporter 2 ORR Overall Response Rate OS Overall survival PAS Pharmacokinetics Analysis Set PFS Progression-Free Survival P-gp P-glycoprotein PgR Progesterone Receptor PICF Patient Informed Consent Form PK Pharmacokinetics PK-ANC PK-Absolute Neutrophil Count PK-QTcF PK-QT Interval in the ECG corrected according to the formula of Fridericia PPS Per-Protocol Set PRO Patient Reported Outcomes PT Prothrombin Time QD Once a day QoL Quality of Life QT QT Interval in the ECG QTc QT Interval in the ECG (corrected) QTcF QT Interval in the ECG (corrected according to the formula of Fridericia) RFS Recurrence-Free Survival RNA Ribonucleic Acid RoW Rest of the World SAE Serious Adverse Event SAP Statistical Analysis Plan SC Steering Committee SEER Surveillance, Epidemiology, and End Results SGOT Serum Glutamic Oxaloacetic Transaminase SGPT Serum Glutamic Pyruvic Transaminase SISH Silver in Situ Hybridization SLN Sentinel Lymph Node STEEP Standardized Definitions for Efficacy End Points (in Adjuvant Breast Cancer Trials) SUSAR Suspected Unexpected Serious Adverse ReactionT1 / 2Half-lifeTBIL Total Bilirubin TdP Torsades de Pointes TEN Toxic Epidermal Necrolysis TmaxThe time at which the maximum observed concentration (Cmax) occurs TNM Tumor, Node and Metastasis ULN Upper Limit of Normal US Ultrasound TRIO Translational Research in Oncology VAS Visual Analogue Scale WBC White Blood Cell WHO World Health Organization PAT059494-WO-PCT Protocol Synopsis Protocol Title A phase III, multicenter, randomized, open-label trial to evaluate efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, early breast cancer (New Adjuvant TriAl with Ribociclib [LEE011]: NATALEE). Trial Number CLEE011O12301C (TRIO033) Trial Sponsor Novartis Participating Approximately 425 sites worldwide will participate in the trial. Sites Investigational Ribociclib (LEE011) Drug Indication Adjuvant treatment of hormone receptor (HR)-positive, HER2-negative, early breast cancer (EBC). Population Pre and postmenopausal women and men with HR-positive, HER2- negative EBC, after adequate surgical resection, who are eligible for adjuvant non-steroidal aromatase inhibitor (NSAI) for at least 5 years. Background EBC and adjuvant treatment of HR-positive, HER2-negative EBC and Rationale Breast cancer (BC) is the most frequently diagnosed cancer worldwide. Approximately 1.7 million new cases of BC and 522,000 deaths attributed to BC were estimated to occur in 2012 worldwide. In the United States, BC was projected to be the most common cancer diagnosed in 2018 with an estimated incidence of 268,670 new cases and 41,400 deaths. Based on Surveillance, Epidemiology, and End Results Program (SEER) data collected between years 1975 and 2012, 93% of cases of BC diagnosed were EBC, with 62% limited to the breast tissue and 31% localized within the breast tissue and regional lymph nodes. Although many patients with EBC may be rendered disease-free with local treatments, distant recurrence due to micro-metastatic disease is common and is the primary cause of death in patients with EBC. It is estimated that 75% of BC express receptors for steroid hormones (estrogen receptor [ER] and / or progesterone receptor [PgR]), and therefore may benefit from adjuvant endocrine therapy (ET) with tamoxifen or aromatase inhibitors (AI) (letrozole, anastrozole or exemestane). ET, independent of chemotherapy, reduces the risk of recurrence and BC deaths in HR-positive EBC. Current clinical guidelines for adjuvant ET in the HR-positive EBC recommend, for premenopausal PAT059494-WO-PCT women, the use of either (a) 5-10 years of tamoxifen with or without ovarian suppression (ovarian suppression is recommended for women with high risk for recurrence after adjuvant chemotherapy), or (b) 5 years of AI with ovarian suppression. Clinical guidelines and expert opinions recommend for postmenopausal women, either (a) initial AI for 5 years (or up to 10 years), or (b) initial tamoxifen for 2-3 years followed by AI either up to total 5 years, or up to 5 years of treatment with AI, or (c) tamoxifen for ~5 years followed by 5 years of AI, or (d) tamoxifen up to 10 years. Limited data on EBC in men suggest that tamoxifen or the combination of an AI with gonadotropin-releasing hormone (GnRH) agonist should be the adjuvant ET of choice. In spite of extensive research and recent advances in a multimodality management of EBC, recurrences are still common, especially in patients with adverse clinical, pathological and genomic features. Approximately 25%-30% of patients with HR-positive, HER2-negative EBC with multiple (≥4) metastatic regional lymph nodes (largely corresponding to Anatomic Stage Group III in the AJCC 8thedition Breast Cancer Staging) will recur within 5 years regardless of treatment; only 48% of these patients will be distant recurrence-free within 20 years and almost half of the patients will die of BC within 20 years despite ET for 5 years. While patients with 1-3 metastatic regional lymph nodes (corresponding generally to Anatomic Stage Group II in the AJCC 8thedition Breast Cancer Staging) may have lower risk of recurrence than patients with Anatomic Stage Group III, still 31% of them will experience distant recurrence and 28% will die from BC within 20 years despite ET. Therefore, new therapeutic strategies are required to improve clinical outcomes in patients with HR-positive, HER2- negative EBC. Clinical experience with ribociclib in advanced BC Ribociclib is an orally bioavailable and highly selective small molecule inhibitor with highly specific nanomolar inhibitory activity against CDK4 / cyclin-D1 and CDK6 / cyclin-D3 enzyme complexes. Ribociclib acts directly on the cyclin D-CDK4 / 6-p16-Rb pathway to block cell-cycle progression, leading to cell cycle arrest. Ribociclib has been approved by a number of regulatory authorities including the United States Food and Drug Administration (FDA) and the European Commission. By the FDA it has been approved in combination with: (1) an AI for the treatment of pre / perimenopausal or PAT059494-WO-PCT postmenopausal women with HR-positive, HER2-negative advanced or metastatic BC, as initial endocrine-based therapy; or (2) fulvestrant for the treatment of postmenopausal women with HR-positive, HER2- negative advanced or metastatic BC, as initial endocrine based therapy or following disease progression on ET. In Europe, ribociclib is indicated for the treatment of women with HR-positive, HER2-negative locally advanced or metastatic BC in combination with an AI or fulvestrant as initial endocrine-based therapy, or in women who have received prior ET. In pre- or perimenopausal women, the ET should be combined with a luteinizing hormone-releasing hormone agonist. Rationale for conducting the trial and for trial design While adjuvant ET for HR-positive EBC is effective in reducing risk of recurrence and improving survival, recurrences are still common, especially in patients with features indicative of an intermediate or high risk of recurrence, like those with Anatomic Stage Groups II and III, among other features. The addition of the CDK4 / 6 inhibitor ribociclib to ET, has proven clinical efficacy with tolerable toxicity profile in HR-positive, HER2-negative advanced BC; therefore, the addition of ribociclib in the adjuvant setting may prolong invasive disease-free survival (iDFS) in patients with HR- positive, HER2-negative EBC with intermediate and high risk for recurrence, by enhancing primary end...

Claims

PAT059494-WO-PCT WHAT IS CLAIMED:

1. A method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient in need thereof, comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle in combination with an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle.

2. A method of preventing or reducing signs or symptoms of early stage breast cancer, comprising administering to the patient a treatment comprising ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof in combination with an aromatase inhibitor, preferably letrozole or anastrozole.

3. The method of claim 2, wherein the the ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, is administered to the patient in a dose ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle.

4. The method of claim 2 or 3, wherein the aromatase inhibitor is administered on every day of the 28-day cycle.

5. A method of preventing or reducing signs or symptoms of early breast cancer, comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle in combination with an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle.

6. The method of any one of claims 1 to 5, wherein the patient is in remission from HR+ / HER2- stage II or stage III early breast cancer.

7. A method of maintaining remission in an adult patient who had previously been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, in combination with an aromatase inhibitor, preferably letrozole or anastrozole.

8. The method of claim 6 or claim 7, wherein the remission is complete remission.

9. The method of claim 6 or claim 7, wherein the remission is partial remission.PAT059494-WO-PCT 10. The method of any one of claims 1 to 9, wherein the treatment reduces recurrence of HR+ / HER2- stage II or stage III early breast cancer.

11. The method of claim 10, wherein the treatment prevents recurrence for at least 3 months.

12. The method of claim 11, wherein the treatment prevents recurrence for at least 6 months.

13. The method of claim 12, wherein the treatment prevents recurrence for at least 1 year.

14. The method of any one of claims 1 to 13, wherein the patient has no signs or symptoms of cancer prior to receiving the treatment.

15. The method of any one of claims 1 to 14, wherein the treatment prevents growth of HR+ / HER2- breast cancer cells.

16. The method of any one of claims 1 to 15, wherein the treatment is an adjuvant therapy.

17. The method of any one of claims 1 to 16, wherein the ribociclib is a pharmaceutically acceptable ribociclib salt.

18. The method of claim 17, wherein the ribociclib salt is ribociclib succinate.

19. The method of any one of claims 1 to 18, wherein the dose of ribociclib is 200 mg / day or 400 mg / day.

20. The method of any one of claims 1 to 18, wherein the ribociclib is not administered at a dose of 600 mg / day.

21. The method of any one of claims 1 to 19, wherein ribociclib is administered as ribociclib succinate, and the total dose of ribociclib is 200 mg / day.

22. The method of any one of claims 1 to 19, wherein ribociclib is administered as ribociclib succinate, and the total dose of ribociclib is 400 mg / day.

23. The method of any one of claims 1 to 19, wherein the ribociclib is administered at a dose of 400 mg / day for a period of time, after which a dose of 200 mg / day ribociclib is administered.

24. The method of any one of claims 1 to 23, wherein the dose of ribociclib is administered orally.PAT059494-WO-PCT 25. The method of any one of claims 1 to 24, wherein the dose of ribociclib is administered in tablet form.

26. The method of any one of claims 1 to 24, wherein the aromatase inhibitor is letrozole or anastrozole.

27. The method of any one of claims 1 to 26, wherein the aromatase inhibitor is administered orally.

28. The method of claim 26 or 27, wherein the letrozole is administered in a dose ranging from 1 mg / day to 4 mg / day.

29. The method of claim 28, wherein the letrozole is administered in a dose of 2.5 mg / day.

30. The method of claim 26 or 27, wherein the anastrozole is administered in a dose ranging from 0.5 mg / day to 1.5 mg / day.

31. The method of claim 30, wherein the anastrozole is administered in a dose of 1 mg / day.

32. The method of any one of claims 1 to 31, wherein the treatment comprises a gonadotropin-releasing hormone agonist.

33. The method of claim 32, wherein the gonadotropin-releasing hormone agonist is goserelin.

34. The method of claim 33, wherein the goserelin is administered in a dose ranging from 2 mg to 5 mg.

35. The method of claim 34, wherein the dose of goserelin is 3.6 mg.

36. The method of any one of claims 33 to 35, wherein the goserelin is administered subcutaneously.

37. The method of any one of claims 33 to 36, wherein the goserelin is administered once every 4 weeks.

38. The method of any one of claims 1 to 31, wherein the patient is a postmenopausal woman.

39. The method of any one of claims 1 to 37, wherein the patient is a premenopausal woman or a man.PAT059494-WO-PCT 40. The method of any one of claims 1 to 39, wherein the treatment is administered to the patient for at least 12 months.

41. The method of claim 40, wherein the treatment is administered to the patient for at least 24 months.

42. The method of claim 40 or claim 41, wherein the treatment is administered to the patient for at least 36 months.

43. The method of any one of claims 40 to 41, wherein the treatment is administered to the patient for at least 48 months.

44. The method of any one of claims 40 to 41, wherein the treatment is administered to the patient for at least 60 months.

45. The method of any one of claims 1 to 44, wherein the treatment continues until the patient has no detectable cancer.

46. The method of any one of claims 1 to 45, wherein the breast cancer is ER+ and PR+.

47. The method of any one of claims 1 to 45, wherein the breast cancer is ER- and PR+.

48. The method of any one of claims 1 to 45, wherein the breast cancer is ER+ and PR-.

49. The method of any one of claims 1 to 48, wherein the breast cancer has a histological subtype that is ductal or a histological subtype that is lobular.

50. The method of any one of claims 1 to 49, wherein the breast cancer is a stage IIA cancer or a stage IIB cancer.

51. The method of claim 50, wherein the breast cancer is a stage IIA cancer.

52. The method of claim 50, wherein the breast cancer is a stage IIB cancer.

53. The method of any one of claims 1 to 49, wherein the breast cancer is a stage IIIA cancer, a stage IIIB cancer, or a stage IIIC cancer.

54. The method of claim 53, wherein the breast cancer is a stage IIIA cancer.

55. The method of claim 53, wherein the breast cancer is a stage IIIB cancer.

56. The method of claim 53, wherein the breast cancer is a stage IIIC cancer.PAT059494-WO-PCT 57. The method of any one of claims 1 to 56, wherein the treatment is administered irrespective of the nodal status of the breast cancer.

58. The method of any one of claims 1 to 57, wherein the breast cancer has a nodal status selected from N0, N1, N2, and N3.

59. The method of claim 57 or 58, wherein the breast cancer has a nodal status of N0.

60. The method of claim 57 or 58, wherein the breast cancer has a nodal status of N1 to N3.

61. The method of claim 57 or 58, wherein the breast cancer has a nodal status of N1.

62. The method of claim 57 or 58, wherein the breast cancer has a nodal status of N2.

63. The method of claim 57 or 58, wherein the breast cancer has a nodal status of N3.

64. The method of any one of claims 1 to 63, wherein the breast cancer comprises one or more cells having a histological grade selected from G1, G2, or G3.

65. The method of claim 64, wherein the breast cancer comprises one or more cells having the histological grade G1.

66. The method of claim 64, wherein the breast cancer comprises one or more cells having the histological grade G2.

67. The method of claim 64, wherein the breast cancer comprises one or more cells having the histological grade G3.

68. The method of any one of claims 1 to 67, wherein the breast cancer comprises a tumor of category T0, T1, T2, T3, or T4.

69. The method of claim 68, wherein the breast cancer comprises a tumor of category T1, T2, or T3.

70. The method of claim 68, wherein the breast cancer comprises a tumor of category T0.

71. The method of claim 68 or 69, wherein the breast cancer comprises a tumor of category T1.

72. The method of claim 68 or 69, wherein the breast cancer comprises a tumor of category T2.PAT059494-WO-PCT 73. The method of claim 68 or 69, wherein the breast cancer comprises a tumor of category T3.

74. The method of claim 68, wherein the breast cancer comprises a tumor of category T4.

75. The method of any one of claims 1 to 74, wherein the breast cancer has a Ki67 status of 20 or lower.

76. The method of any one of claims 1 to 74, wherein the breast cancer has a Ki67 status of greater than 20.

77. The method of any one of claims 1 to 76, wherein prior to the administration, the patient has received a loading dose of (i) ribociclib and / or (ii) an endocrine therapy.

78. The method of any one of claims 1 to 77, wherein the patient has received at least one prior treatment for cancer.

79. The method of claim 78, wherein the prior treatment is an adjuvant treatment after another prior treatment.

80. The method of claim 78 or 79, wherein the prior treatment is surgery.

81. The method of claim 80, wherein the surgery comprises a complete surgical resection of the cancer.

82. The method of claim 80 or 81, wherein the surgery is a mastectomy.

83. The method of claim 80 or 81, wherein the prior treatment is a chemotherapy.

84. The method of claim 83, wherein the prior treatment is an adjuvant chemotherapy.

85. The method of claim 83, wherein the prior treatment is a neoadjuvant chemotherapy.

86. The method of claim 78 or 79, wherein the prior treatment is an endocrine therapy.

87. The method of claim 78 or 79, wherein the prior treatment is radiation therapy.

88. The method of any one of claims 78 to 87, wherein the patient did not respond to the prior treatment.

89. The method of any one of claims 1 to 88, wherein the patient is located in a geographic region selected from North America, Western Europe, or Oceania.PAT059494-WO-PCT 90. The method of any one of claims 1 to 89, wherein the patient is Asian.

91. The method of any one of claims 1 to 90, wherein the patient is 18 to 45 years of age.

92. The method of any one of claims 1 to 90, wherein the patient is 45 to 54 years of age.

93. The method of any one of claims 1 to 90, wherein the patient is 54 to 64 years of age.

94. The method of any one of claims 1 to 90, wherein the patient is greater than 64 years of age.

95. The method of any one of claims 1 to 94, wherein the patient has a BMI of 25 or higher.

96. The method of any one of claims 1 to 94, wherein the patient has a BMI lower than 25.

97. The method of any one of claims 1 to 96, wherein the treatment improves a condition of the patient relative to a patient not receiving the treatment and / or relative to the condition in the patient prior to treatment.

98. The method of any one of claims 1 to 97, wherein the treatment reduces the risk of invasive disease.

99. The method of claim 98, wherein the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than 1 when the risk is calculated relative to patients not receiving the treatment.

100. The method of claim 99, wherein the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.78 when the risk is calculated relative to patients not receiving the treatment.

101. The method of any one of claims 1 to 37 and 39 to 100, wherein the patient is a premenopausal woman or a man and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.72 when the risk is calculated relative to patients receiving the treatment.

102. The method of any one of claims 98 to 100, wherein the patient has HR+ / HER2- stage III early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.74 when the risk is calculated relative to patients not receiving the treatment.PAT059494-WO-PCT 103. The method of any one of claims 98 to 100, wherein the patient has HR+ / HER2- stage II early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.76 when the risk is calculated relative to patients not receiving the treatment.

104. The method of any one of claims 98 to 100, wherein the patient has HR+ / HER2- stage III early breast cancer, and the treatment yields at least a 25% reduction in the risk of invasive disease corresponding to a hazard ratio of 0.75 when the risk is calculated relative to patients not receiving the treatment.

105. The method of any one of claims 1 to 104, wherein the treatment reduces the risk of invasive disease to a similar level for patient subgroups comprising patients with stage II early breast cancer, stage III early breast cancer, patients who are premenopausal women or men, and patients who are postmenopausal women.

106. The method of any one of claims 1 to 105, wherein the treatment yields no deterioration in overall survival corresponding to a hazard ratio of 0.76 when the risk is calculated relative to patients not receiving the treatment.

107. The method of one of claims 1 to 106, wherein the treatment reduces and / or prevents one or more of recurrence of the cancer, spread of the cancer, development and / or growth of an additional cancer, and risk of death from the cancer.

108. The method of claim 107, wherein the treatment reduces the recurrence of cancer, wherein the recurrence is one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, and distant recurrence.

109. The method of claim 107 or claim 108, wherein the treatment reduces the spread of cancer, wherein the spread of cancer is an invasive contralateral breast cancer or an additional primary invasive cancer.

110. The method of any one of claims 1 to 109, wherein the treatment prevents death from cancer.

111. A method of maintaining in remission an adult patient who had previously been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient a treatment comprising administering to the patient a treatment comprising a dose of ribociclib, a freebase form thereof or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-PAT059494-WO-PCT day cycle in combination with an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle.

112. A method of preventing breast cancer recurrence in an adult patient, comprising providing adjuvant treatment to a patient who has received a prior treatment for HR+ / HER2- stage II or III early breast cancer, wherein the adjuvant treatment comprises administering to the patient 400 mg ribociclib or a pharmaceutically acceptable salt thereof on days 1 to 21 of a 28-day cycle for at least 36 months, in combination with an aromatase inhibitor as defined in any one of claims 26 to 31 administered on every day of the 28-day cycle.

113. The method of claim 112, wherein the prior treatment is surgical resection of the cancer.

114. Ribociclib or a pharmaceutically acceptable salt thereof and an aromatase inhibitor for use in a method of treatment for HR+ / HER2- stage II or III early breast cancer in an adult patient, wherein the method is the method of any one of claims 1 to 112.

115. The use of ribociclib or a pharmaceutically acceptable salt thereof and an aromatase inhibitor in the manufacture of a medicament for treating HR+ / HER2- stage II or III early breast cancer in an adult patient, wherein the medicament is administered by the method of any one of claims 1 to 112.

116. A kit for performing a method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient according to any one of claims 1 to 112.

117. A method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient in remission, comprising administering to the adult patient ribociclib in combination with an aromatase inhibitor whereby the administration maintains the adult patient in remission for at least 3 months.

118. A method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient, comprising providing adjuvant treatment by administering ribociclib in combination with an aromatase inhibitor, wherein the patient at start of the adjuvant treatment is in complete remission, and the administration of ribociclib in combination with aromatase inhibitor maintains the adult patient in complete remission for at least 3 months.

119. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 6 months.PAT059494-WO-PCT 120. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 9 months.

121. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 12 months.

122. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 15 months.

123. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 18 months.

124. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 21 months.

125. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 24 months.

126. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 27 months.

127. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 30 months.

128. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 33 months.

129. The method of claim 117 or 118, wherein the administration maintains the adult patient in complete remission for at least 36 months.

130. The method of any one of claims 117 to 129, wherein ribociclib and aromatase inhibitor are administered for a treatment duration, and the administration maintains the adult patient in complete remission for at least the treatment duration.

131. The method of any one of claims 117 to 129, wherein a dose of 400 mg ribociclib is orally administered once daily on days 1-21 of a 28-day cycle and aromatase inhibitor is administered once daily on each day of the 28-day cycle.

132. The method of any one of claims 117 to 129, wherein a dose of 400 mg ribociclib is orally administered once daily on days 1-21 of a 28-day cycle for a treatment duration ofPAT059494-WO-PCT up to three years and aromatase inhibitor is administered once daily on each day of the 28-day cycle for the up to three years.

133. The method of any one of claims 117 to 129, wherein a dose of 400 mg ribociclib is orally administered once daily on days 1-21 of a 28-day cycle for a treatment duration of up to five years and aromatase inhibitor is administered once daily on each day of the 28-day cycle for the up to five years.

134. The method of any one of claims 117 to 133, wherein a pharmaceutically acceptable salt of ribociclib is orally administered in an amount corresponding to 400 mg ribociclib.

135. The method of claim 134, wherein the pharmaceutically acceptable salt is ribociclib succinate.

136. The method of any one of claims 117 to 135, wherein the adult patient was never treated with a 600 mg dose of ribociclib.

137. The method of any one of claims 117 to 136, wherein the adult patient has never been diagnosed with HR+ / HER2- advanced or metastatic breast cancer.

138. The method of any one of claims 117 to 137, wherein ribociclib and aromatase inhibitor are administered as adjuvant therapy.

139. The method of claim any one of claims 117 to 138, wherein the ribociclib is not administered at a dose of 600 mg / day.

140. The method of any one of claims 117 to 139, wherein the dose of ribociclib is administered in tablet form.

141. The method of any one of claims 117 to 139, wherein two tablets are orally administered to the adult patient once daily on days 1-21 of a 28 day cycle repeating for a treatment duration, and each tablet contains an amount of a pharmaceutically acceptable ribociclib salt corresponding to 200 mg ribociclib.

142. The method of claim 141, wherein the ribociclib salt is ribociclib succinate.

143. The method of any one of claims 117 to 142, wherein the aromatase inhibitor is letrozole.

144. The method of any one of claims 117 to 142, wherein the aromatase inhibitor is anastrazole.PAT059494-WO-PCT 145. The method of any one of claims 117 to 144, wherein the aromatase inhibitor is letrozole, and the letrozole is administered in a dose ranging from 1 mg to 4 mg once daily.

146. The method of any one of claims 117 to 144, the aromatase inhibitor is letrozole, and the letrozole is administered in a dose of 2.5 mg once daily.

147. The method of any one of claims 117 to 144, wherein the aromatase inhibitor is anastrozole, and the anastrozole is administered in a dose ranging from 0.5 mg once daily to 1.5 mg once daily.

148. The method of any one of claims 117 to 144, wherein the aromatase inhibitor is anastrozole, and the anastrozole is administered in a dose of 1mg once daily.

149. The method of any one of claims 117 to 148, further comprising administering to the adult patient a gonadotropin-releasing hormone agonist.

150. The method of claim 149, wherein the gonadotropin-releasing hormone agonist is goserelin.

151. The method of claim 150, wherein the goserelin is administered in a dose ranging from 2 mg to 5 mg.

152. The method of claim 151, wherein the dose of goserelin is 3.6 mg.

153. The method of any one of claims 150 to 152, wherein the goserelin is administered subcutaneously.

154. The method of any one of claims 150 to 153, wherein the goserelin is administered once every 4 weeks.

155. The method of any one of claims 117 to 148, wherein the patient is a postmenopausal woman.

156. The method of any one of claims 117 to 154, wherein the patient is a premenopausal woman or a man.

157. The method of any one of claims 117 to 156, wherein the breast cancer has a histological subtype that is ductal or a histological subtype that is lobular.

158. The method of any one of claims 117 to 156, wherein the breast cancer is a stage IIA cancer or a stage IIB cancer.PAT059494-WO-PCT 159. The method of any one of claims 117 to 156, wherein the breast cancer is a stage IIA cancer.

160. The method of any one of claims 117 to 156, wherein the breast cancer is a stage IIB cancer.

161. The method of any one of claims 117 to 156, wherein the breast cancer is a stage IIIA cancer, a stage IIIB cancer, or a stage IIIC cancer.

162. The method of any one of claims 117 to 156, wherein the breast cancer is a stage IIIA cancer.

163. The method of any one of claims 117 to 156, wherein the breast cancer is a stage IIIB cancer.

164. The method of any one of claims 117 to 156, wherein the breast cancer is a stage IIIC cancer.

165. The method of any one of claims 117 to 156, wherein the treatment is administered irrespective of the nodal status of the breast cancer.

166. The method of any one of claims 117 to 156, wherein treatment with ribociclib and aromatase inhibitor is not adjusted on the basis of the nodal status of the early breast cancer.

167. The method of any one of claims 117 to 156, wherein the breast cancer has a nodal status selected from N0, N1, N2, and N3.

168. The method of any one of claims 117 to 156, wherein the breast cancer has a nodal status of N0.

169. The method of any one of claims 117 to 156, wherein the breast cancer has a nodal status of N1-N3.

170. The method of any one of claims 117 to 156, wherein the breast cancer has a nodal status of N1.

171. The method of any one of claims 117 to 156, wherein the breast cancer has a nodal status of N2.PAT059494-WO-PCT 172. The method of any one of claims 117 to 156, wherein the breast cancer has a nodal status of N3.

173. The method of any one of claims 117 to 156, wherein the breast cancer comprises one or more cells having a histological grade selected from G1, G2, or G3.

174. The method of any one of claims 117 to 156, wherein the breast cancer comprises one or more cells having the histological grade G1.

175. The method of any one of claims 117 to 156, wherein the breast cancer comprises one or more cells having the histological grade G2.

176. The method of any one of claims 117 to 156, wherein the breast cancer comprises one or more cells having the histological grade G3.

177. The method of any one of claims 117 to 156, wherein the breast cancer comprises a tumor of category T0, T1, T2, T3, or T4.

178. The method of any one of claims 117 to 156, wherein the breast cancer comprises a tumor of category T1, T2, or T3.

179. The method of any one of claims 117 to 156, wherein the breast cancer comprises a tumor of category T0.

180. The method of any one of claims 117 to 156, wherein the breast cancer comprises a tumor of category T1.

181. The method of any one of claims 117 to 156, wherein the breast cancer comprises a tumor of category T2.

182. The method of any one of claims 117 to 156, wherein the breast cancer comprises a tumor of category T3.

183. The method of any one of claims 117 to 156, wherein the breast cancer comprises a tumor of category T4.

184. The method of any one of claims 117 to 156, wherein the breast cancer has a Ki67 status of 20 or lower.

185. The method of any one of claims 117 to 156, wherein the breast cancer has a Ki67 status of greater than 20.PAT059494-WO-PCT 186. The method of any one of claims 117 to 185, wherein prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had surgery for the early breast cancer.

187. The method of any one of claims 117 to 185, wherein prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had (1) surgery for the early breast cancer, followed by (2) chemotherapy.

188. The method of any one of claims 117 to 185, wherein prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had (1) surgery for the early breast cancer, followed by (2) chemotherapy and / or endocrine therapy.

189. The method of claim 188, wherein the endocrine therapy was therapy with a prior aromatase inhibitor.

190. The method of claim 188, wherein the prior aromatase inhibitor was letrozole or anastrozole.

191. The method of any one of claims 117 to 185, wherein immediately prior to administering ribociclib and aromatase inhibitor to the adult patient, the patient had surgery for the early breast cancer.

192. The method of any one of claims 186 to 191, wherein the surgery comprised a complete surgical resection of the cancer.

193. The method of any one of claims 186 to 191, wherein the surgery was a mastectomy.

194. The method of any one of claims 186 to 191, wherein the patient received neoadjuvant therapy.

195. The method of claim 194, wherein the neoadjuvant therapy was chemotherapy.

196. The method of any one of claims 117 to 195, wherein the adult patient is located in a geographic region selected from North America, Western Europe, or Oceania.

197. The method of any one of claims 117 to 195, wherein the patient is Asian.

198. The method of any one of claims 117 to 195, wherein the patient is 18 to 45 years of age.

199. The method of any one of claims 117 to 195, wherein the patient is 45 to 54 years of age.

200. The method of any one of claims 117 to 195, wherein the patient is 54 to 64 years of age.PAT059494-WO-PCT 201. The method of any one of claims 117 to 195, wherein the patient is greater than 64 years of age.

202. The method of any one of claims 117 to 195, wherein the patient has a BMI of 25 or higher.

203. The method of any one of claims 117 to 195, wherein the patient has a BMI lower than 25.

204. The method of any one of claims 117 to 203, wherein the treatment improves a condition of the patient relative to a patient not receiving the treatment and / or relative to the condition in the patient prior to treatment.

205. The method of any one of claims 117 to 203, wherein the treatment reduces the risk of invasive disease.

206. The method of any one of claims 117 to 203, wherein the treatment reduces the risk of invasive disease in the adult patient corresponding to a hazard ratio of less than 1 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib.

207. The method any one of claims 117 to 203, wherein the treatment reduces the risk of invasive disease in the adult patient corresponding to a hazard ratio of less than or equal to 0.78 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib.

208. The method of any one of claims 117 to 203, wherein the adult patient is a premenopausal woman or a man and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.72 when the risk is calculated relative to other premenopausal women or men, respectively, having received the same treatment as the premenopausal woman or man, respectively, except that the other premenopausal women or men did not receive the ribociclib.

209. The method of any one of claims 117 to 203, wherein the adult patient was diagnosed with HR+ / HER2- stage III early breast cancer and the treatment reduces the risk of invasive disease in the adult patient corresponding to a hazard ratio of less than or equal to 0.74 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib.

210. The method of any one of claims 117 to 203, wherein the adult patient was diagnosed with HR+ / HER2- stage II early breast cancer and the treatment reduces the risk of invasivePAT059494-WO-PCT disease corresponding to a hazard ratio of less than or equal to 0.76 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib.

211. The method of any one of claims 117 to 203, wherein the adult patient was diagnosed with HR+ / HER2- stage III early breast cancer, and the treatment yields at least a 25% reduction in the risk of invasive disease corresponding to a hazard ratio of 0.75 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib.

212. The method of any one of claims 117 to 203, wherein the treatment reduces the risk of invasive disease to a similar level for patient subgroups comprising patients with stage II early breast cancer, stage III early breast cancer, patients who are premenopausal women or men, and patients who are postmenopausal women.

213. The method of any one of claims 117 to 203, wherein the treatment yields no deterioration in overall survival corresponding to a hazard ratio of 0.76 when the risk is calculated relative to other patients having received the same treatment as the adult patient except that the other patients did not receive the ribociclib.

214. The method of one of claims 117 to 203, wherein the treatment reduces and / or prevents one or more of recurrence of the cancer, spread of the cancer, development and / or growth of an additional cancer, and risk of death from the cancer.

215. The method of one of claims 117 to 203, wherein the treatment reduces the recurrence of cancer, wherein the recurrence is one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, and distant recurrence.

216. The method of one of claims 117 to 203, wherein the treatment reduces the spread of cancer, wherein the spread of cancer is an invasive contralateral breast cancer or an additional primary invasive cancer.

217. Ribociclib or a pharmaceutically acceptable salt thereof and an aromatase inhibitor for use in a method of treatment for HR+ / HER2- stage II or III early breast cancer in an adult patient, wherein the method is the method of any one of claims 117 to 216.

218. The use of ribociclib or a pharmaceutically acceptable salt thereof and an aromatase inhibitor in the manufacture of a medicament for treating HR+ / HER2- stage II or III earlyPAT059494-WO-PCT breast cancer in an adult patient, wherein the medicament is administered by the method of any one of claims 117 to 216.

219. A kit for performing a method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient according to any one of claims 117 to 216.

220. A method of treating an adult patient who has been diagnosed with HER+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle, wherein the method results in an improvement in the patient in one or more of their overall survival (OS), distant disease- free survival (DDFS), or recurrence free survival (RFS).

221. A method for improving one or more of overall survival (OS), distant disease-free survival (DDFS), or recurrence free survival (RFS) in a patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle.

222. A method for reducing the risk of local or regional invasive recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle.

223. A method for reducing the risk of invasive recurrence of early breast cancer in one or more of the bone, liver, and lung or pleura of an adult patient, who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle.

224. The method of any of claims 220 to 223, wherein the treatment is administered irrespective of the nodal status of the breast cancer.PAT059494-WO-PCT 225. A method for reducing the risk of recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day on days 1-21 of a 28-day cycle and (ii) an aromatase inhibitor administered on every day of the 28-day cycle, wherein the treatment is administered irrespective of the nodal status of the breast cancer.

226. The method of any of claims 220 to 225, wherein the breast cancer has a nodal status of N0, N1, N2 or N3.

227. The method of claim 226, wherein the breast cancer has a nodal status of N0.

228. The method of any of claims 220 to 227, wherein the early breast cancer is stage II, for example stage IIA.

229. The method of any of claims 220 to 227, wherein the early breast cancer is stage III, for example stage IIIB or IIIC.

230. The method of any of claims 220 to 229, wherein the breast cancer is of the ductal subtype.

231. The method of any of claims 220 to 230, wherein the patient is Asian.

232. The method of any of claims 220 to 231, wherein the method is an adjuvant treatment because the patient has received at least one prior treatment for breast cancer selected from the group consisting of surgery, chemotherapy, and radiation therapy.

233. The method of claim 232, wherein the patient has not had a mastectomy.

234. The method of any of claims 220 to 233, wherein the dose of ribociclib is 400 mg / day.

235. The method of any of claims 220 to 234, wherein the ribociclib is administered in the form of a salt, preferably as ribociclib succinate.

236. The method of any of claims 220 to 235, wherein the aromatase inhibitor is letrozole or anastrozole.

237. The method of claim 236, wherein the aromatase inhibitor is letrozole, preferably administered in a dose of 2.5 mg / day.PAT059494-WO-PCT 238. The method of claim 236, wherein the aromatase inhibitor is anastrozole, preferably administered in a dose of 1 mg / day.

239. The method of any of claims 220 to 238, wherein the dose of ribociclib is 400 mg / day, the ribociclib is administered in the form of ribociclib succinate, and the aromatase inhibitor is letrozole or anastrozole, preferably 2.5 mg / day of letrozole or 1 mg / day anastrozole.

240. The method of any of claims 220 to 239, wherein the improvement in OS, DDFS and / or RFS, or the reduction in the risk of recurrence of the breast cancer, are achieved in the patient for at least 36 months.

241. Ribociclib for use in a method of improving one or more of overall survival (OS), distant disease-free survival (DDFS), or recurrence free survival (RFS) in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle.

242. Ribociclib for use in a method of reducing the risk of local or regional invasive recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle.

243. Ribociclib for use in a method of reducing the risk of invasive recurrence of early breast cancer in one or more of the bone, liver, and lung or pleura of an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28-day cycle.

244. Ribociclib for use in accordance with any of claims 241 to 243, wherein the treatment is administered irrespective of the nodal status of the breast cancer.PAT059494-WO-PCT 245. Ribociclib for use in a method of reducing the risk of recurrence of early breast cancer in an adult patient who has been diagnosed with HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib ranging from 150 mg / day to 450 mg / day administered on days 1- 21 of a 28-day cycle, and (ii) an aromatase inhibitor administered on every day of the 28- day cycle, wherein the treatment is administered irrespective of the nodal status of the breast cancer.

246. Ribociclib for use according to any of claims 241 to 245, wherein the breast cancer has a nodal status of N0, N1, N2 or N3.

247. Ribociclib for use according to claim 246, wherein the breast cancer has a nodal status of N0.

248. Ribociclib for use according to any of claims 241 to 247, wherein the early breast cancer is stage II, such as stage IIA.

249. Ribociclib for use according to any of claims 241 to 247, wherein the early breast cancer is stage III, such as stage IIIB or IIIC.

250. Ribociclib for use according to any of claims 241 to 249, wherein the breast cancer is of the ductal subtype.

251. Ribociclib for use according to any of claims 241 to 250, wherein the patient is Asian.

252. Ribociclib for use according to any of claims 241 to 251, wherein the method is an adjuvant treatment because the patient has received at least one prior treatment for breast cancer selected from the group consisting of surgery, chemotherapy, and radiation therapy.

253. Ribociclib for use according to claim 252, wherein the patient has not had a mastectomy.

254. Ribociclib for use according to any of claims 241 to 253, wherein the dose of ribociclib is 400 mg / day.

255. Ribociclib for use according to any of claims 241 to 254, wherein the ribociclib is administered in the form of a salt, preferably as ribociclib succinate.

256. Ribociclib for use according to any of claims 241 to 255, wherein the aromatase inhibitor is letrozole or anastrozole.PAT059494-WO-PCT 257. Ribociclib for use according to claim 256, wherein the aromatase inhibitor is letrozole, preferably administered in a dose of 2.5 mg / day.

258. Ribociclib for use according to claim 256, wherein the aromatase inhibitor is anastrozole, preferably administered in a dose of 1 mg / day.

259. Ribociclib for use according to any of claims 241 to 258, wherein the dose of ribociclib is 400 mg / day, the ribociclib is administered in the form of ribociclib succinate, and the aromatase inhibitor is letrozole or anastrozole, preferably 2.5 mg / day of letrozole or 1 mg / day anastrozole.

260. Ribociclib for use according to any of claims 241 to 259, wherein the improvement in OS, DDFS and / or RFS, or the reduction in the risk of recurrence of the breast cancer, are achieved in the patient for at least 36 months.

261. Ribociclib succinate for use in a method of treatment of HR+ / HER2- stage II or stage III early breast cancer in an adult patient who has received at least one prior treatment for early breast cancer and has no signs or symptoms of cancer, wherein the method comprises administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1 to 21 of a 28-day cycle, and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle.

262. Ribociclib succinate for use according to claim 261, wherein the adjuvant treatment comprises a dose of 2.5 mg / day letrozole.

263. Ribociclib succinate for use according to claim 261, wherein the adjuvant treatment comprises a dose of 1 mg / day anastrozole.

264. Ribociclib succinate for use according to any one of claims 261 to 263, wherein the breast cancer has a nodal status of N0, N1, N2 or N3.

265. Ribociclib succinate for use according to claim 264, wherein the breast cancer has a nodal status of N0.

266. Ribociclib succinate for use according to any one of claims 261 to 265, wherein the early breast cancer is stage II, such as stage IIA.

267. Ribociclib succinate for use according to any one of claims 261 to 265, wherein the early breast cancer is stage III, such as stage IIIB.PAT059494-WO-PCT 268. Ribociclib succinate for use according to any one of claims 261 to 265, wherein the early breast cancer is stage III, such as IIIC.

269. Ribociclib succinate for use according to any one of claims 261 to 268, wherein the breast cancer is of the ductal subtype.

270. Ribociclib succinate for use according to any one of claims 261 to 269, wherein the patient is Asian.

271. Ribociclib succinate for use according to any one of claims 261 to 270, wherein the method is an adjuvant treatment because the patient has received at least one prior treatment for breast cancer selected from the group consisting of surgery, chemotherapy, endocrine therapy, and radiation therapy.

272. Ribociclib succinate for use according to claim 271, wherein the patient has not had a mastectomy.

273. Ribociclib succinate for use according to any one of claims 261 to 272, wherein the method improves overall survival (OS), distant disease-free survival (DDFS), and / or recurrence free survival (RFS) of the breast cancer in the patient for at least 36 months; or the method reduces the risk of recurrence of the breast cancer in the patient for at least 36 months.

274. A method of preventing recurrence of breast cancer in an adult patient who has received a prior treatment for HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, and (ii) a dose of an aromatase inhibitor, preferably letrozole or anastrozole.

275. A method of treating an adult patient in remission from HR+ / HER2- stage II or stage III early breast cancer, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, and (ii) a dose of an aromatase inhibitor, preferably letrozole or anastrozole.

276. A method of treating HR+ / HER2- stage II or stage III early breast cancer in an adult patient in need thereof, comprising administering to the patient (i) a dose of ribociclib, a freebase form thereof, or a pharmaceutically acceptable salt thereof, ranging from 150 mg / day to 450 mg / day administered on days 1-21 of a 28-day cycle and (ii) an aromatase inhibitor, preferably letrozole or anastrozole, administered on every day of the 28-day cycle.PAT059494-WO-PCT 277. The method of any one of claims 274 to 276, wherein the ribociclib is a pharmaceutically acceptable ribociclib salt.

278. The method of claim 277, wherein the ribociclib salt is ribociclib succinate.

279. The method of any one of claims 274, 275, 277, and 278, wherein the dose of ribociclib is not 600 mg / day.

280. The method of any one of claims 274 to 278, wherein the dose of ribociclib is 200 mg / day or 400 mg / day.

281. The method of claim 280, wherein ribociclib is administered as ribociclib succinate, and the total dose of ribociclib is 200 mg / day.

282. The method of claim 280, wherein ribociclib is administered as ribociclib succinate, and the total dose of ribociclib is 400 mg / day.

283. The method of claim 280, wherein the ribociclib is administered at a dose of 400 mg / day for a period of time, after which a dose of 200 mg / day ribociclib is administered.

284. The method of any one of claims 274 to 283, wherein the dose of ribociclib is administered orally.

285. The method of any one of claims 274 to 284, wherein the dose of ribociclib is administered in tablet form.

286. The method of any one of claims 274 to 285, wherein the aromatase inhibitor is letrozole or anastrozole.

287. The method of any one of claims 274 to 286, wherein the aromatase inhibitor is administered orally.

288. The method of claim 286 or 287, wherein the letrozole is administered in a dose ranging from 1 mg / day to 4 mg / day.

289. The method of claim 288, wherein the letrozole is administered in a dose of 2.5 mg / day.

290. The method of claim 286 or 287, wherein the anastrozole is administered in a dose ranging from 0.5 mg / day to 1.5 mg / day.

291. The method of claim 290, wherein the anastrozole is administered in a dose of 1 mg / day.PAT059494-WO-PCT 292. A method of treating breast cancer recurrence in an adult patient who has received at least one prior treatment for HR+ / HER2- stage II or III early breast cancer and who has no detectable signs or symptoms of breast cancer, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1 to 21 of a 28-day cycle, and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle.

293. A method of treating an adult patient who is in remission from HR+ / HER2- stage II or stage III early breast cancer and in need of adjuvant treatment, comprising administering to the patient an adjuvant treatment comprising (i) a dose of ribociclib succinate at a total dose of ribociclib of 400 mg / day administered on days 1-21 of a 28-day cycle and (ii) a dose of either 2.5 mg / day letrozole or 1 mg / day anastrozole administered on every day of the 28-day cycle.

294. The method of any one of claims 274 to 293, wherein the treatment further comprises administering a gonadotropin-releasing hormone agonist.

295. The method of claim 294, wherein the gonadotropin-releasing hormone agonist is goserelin.

296. The method of claim 295, wherein the goserelin is administered in a dose ranging from 2 mg to 5 mg.

297. The method of claim 296, wherein the dose of goserelin is 3.6 mg.

298. The method of any one of claims 294 to 297, wherein the goserelin is administered subcutaneously.

299. The method of any one of claims 294 to 298, wherein the goserelin is administered once every 4 weeks.

300. The method of any one of claims 274 to 299, wherein the patient is a postmenopausal woman.

301. The method of any one of claims 274 to 293, wherein the patient is a premenopausal woman or a man.

302. The method of any one of claims 274 to 301, wherein the treatment is administered to the patient for at least 12 months.PAT059494-WO-PCT 303. The method of claim 302, wherein the treatment is administered to the patient for at least 24 months.

304. The method of claim 302 or 303, wherein the treatment is administered to the patient for at least 36 months.

305. The method of any one of claims 302 to 304, wherein the treatment is administered to the patient for at least 48 months.

306. The method of any one of claims 302 to 305, wherein the treatment is administered to the patient for at least 60 months.

307. The method of any one of claims 274 to 306, wherein the breast cancer is ER+ and PR+.

308. The method of any one of claims 274 to 306, wherein the breast cancer is ER- and PR+.

309. The method of any one of claims 274 to 306, wherein the breast cancer is ER+ and PR-.

310. The method of any one of claims 274 to 309, wherein the breast cancer has a histological subtype that is ductal.

311. The method of any one of claims 274 to 310, wherein the breast cancer has a histological subtype that is lobular.

312. The method of any one of claims 274 to 311, wherein the breast cancer is a stage IIA cancer or a stage IIB cancer.

313. The method of claim 312, wherein the breast cancer is a stage IIA cancer.

314. The method of claim 312, wherein the breast cancer is a stage IIB cancer.

315. The method of any one of claims 274 to 311, wherein the breast cancer is a stage IIIA cancer, a stage IIIB cancer, or a stage IIIC cancer.

316. The method of claim 315, wherein the breast cancer is a stage IIIA cancer.

317. The method of claim 315, wherein the breast cancer is a stage IIIB cancer.

318. The method of claim 315, wherein the breast cancer is a stage IIIC cancer.

319. The method of any one of claims 274 to 318, wherein the treatment is administered irrespective of the nodal status of the breast cancer.PAT059494-WO-PCT 320. The method of any one of claims 274 to 319, wherein the breast cancer has a nodal status selected from N0, N1, N2, and N3.

321. The method of claim 319 or 320, wherein the breast cancer has a nodal status of N0.

322. The method of claim 319 or 320, wherein the breast cancer has a nodal status of N1 to N3.

323. The method of claim 319 or 320, wherein the breast cancer has a nodal status of N1.

324. The method of claim 319 or 320, wherein the breast cancer has a nodal status of N2.

325. The method of claim 319 or 320, wherein the breast cancer has a nodal status of N3.

326. The method of any one of claims 274 to 325, wherein the breast cancer comprises one or more cells having a histological grade selected from G1, G2, or G3.

327. The method of claim 326, wherein the breast cancer comprises one or more cells having the histological grade G1.

328. The method of claim 326, wherein the breast cancer comprises one or more cells having the histological grade G2.

329. The method of claim 326, wherein the breast cancer comprises one or more cells having the histological grade G3.

330. The method of any one of claims 274 to 329, wherein the breast cancer comprises a tumor of category T0, T1, T2, T3, or T4.

331. The method of claim 330, wherein the breast cancer comprises a tumor of category T1, T2, or T3.

332. The method of claim 330, wherein the breast cancer comprises a tumor of category T0.

333. The method of claim 330 or claim 331, wherein the breast cancer comprises a tumor of category T1.

334. The method of claim 330 or claim 331, wherein the breast cancer comprises a tumor of category T2.

335. The method of claim 330 or claim 331, wherein the breast cancer comprises a tumor of category T3.

336. The method of claim 330, wherein the breast cancer comprises a tumor of category T4.PAT059494-WO-PCT 337. The method of any one of claims 274 to 336, wherein the breast cancer has a Ki67 status of 20 or lower.

338. The method of any one of claims 274 to 336, wherein the breast cancer has a Ki67 status of greater than 20.

339. The method of any one of claims 274 to 338, wherein prior to the administration, the patient has received a loading dose of (i) ribociclib and / or (ii) an endocrine therapy.

340. The method of any one of claims 274 to 291 and 293 to 339, wherein the patient has received at least one prior treatment for cancer.

341. The method of claim 292 or claim 340, wherein the prior treatment is an adjuvant treatment after another prior treatment.

342. The method of claim 340 or 341, wherein the prior treatment is surgery.

343. The method of claim 342, wherein the surgery comprises a complete surgical resection of the cancer.

344. The method of claim 342 or claim 343, wherein the surgery is a mastectomy.

345. The method of claim 340 or claim 341, wherein the prior treatment is a chemotherapy.

346. The method of claim 345, wherein the prior treatment is an adjuvant chemotherapy.

347. The method of claim 345, wherein the prior treatment is a neoadjuvant chemotherapy.

348. The method of claim 340 or claim 341, wherein the prior treatment is an endocrine therapy.

349. The method of claim 340 or claim 341, wherein the prior treatment is radiation therapy.

350. The method of any one of claims 292 and 340 to 349, wherein the patient did not respond to the prior treatment.

351. The method of any one of claims 274 to 350, wherein the patient is located in a geographic region selected from North America, Western Europe, or Oceania.

352. The method of any one of claims 274 to 351, wherein the patient is Asian.

353. The method of any one of claims 274 to 352, wherein the patient is 18 to 45 years of age.PAT059494-WO-PCT 354. The method of any one of claims 274 to 352, wherein the patient is 45 to 54 years of age.

355. The method of any one of claims 274 to 352, wherein the patient is 54 to 64 years of age.

356. The method of any one of claims 274 to 352, wherein the patient is greater than 64 years of age.

357. The method of any one of claims 274 to 357, wherein the patient has a BMI of 25 or higher.

358. The method of any one of claims 274 to 357, wherein the patient has a BMI lower than 25.

359. The method of any one of claims 274 to 358, wherein the treatment improves a condition of the patient relative to a patient not receiving the treatment and / or relative to the condition in the patient prior to treatment.

360. The method of any one of claims 274 to 359, wherein the treatment reduces the risk of invasive disease.

361. The method of claim 360, wherein the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than 1 when the risk is calculated relative to patients not receiving the treatment.

362. The method of claim 361, wherein the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.78 when the risk is calculated relative to patients not receiving the treatment.

363. The method of any one of claims 274 to 299 and 301 to 362, wherein the patient is a premenopausal woman or a man and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.72 when the risk is calculated relative to patients receiving the treatment.

364. The method of any one of claims 360 to 362, wherein the cancer is HR+ / HER2- stage III early breast cancer and the treatment reduces the risk of invasive disease corresponding to a hazard ratio of less than or equal to 0.74 when the risk is calculated relative to patients not receiving the treatment.

365. The method of any one of claims 360 to 362, wherein the cancer is HR+ / HER2- stage II early breast cancer and the treatment reduces the risk of invasive diseasePAT059494-WO-PCT corresponding to a hazard ratio of less than or equal to 0.76 when the risk is calculated relative to patients not receiving the treatment.

366. The method of any one of claims 360 to 362, wherein the cancer is HR+ / HER2- stage III early breast cancer, and the treatment yields at least a 25% reduction in the risk of invasive disease corresponding to a hazard ratio of 0.75 when the risk is calculated relative to patients not receiving the treatment.

367. The method of any one of claims 360 to 366, wherein the treatment reduces the risk of invasive disease to a similar level for patient subgroups comprising patients with stage II early breast cancer, stage III early breast cancer, patients who are premenopausal women or men, and patients who are postmenopausal women.

368. The method of any one of claims 274 to 367, wherein the treatment yields no deterioration in overall survival corresponding to a hazard ratio of 0.76 when the risk is calculated relative to patients not receiving the treatment.

369. The method of any one of claims 274 to 368, wherein the treatment reduces and / or prevents one or more of recurrence of the cancer, spread of the cancer, development and / or growth of an additional cancer, and risk of death from the cancer.

370. The method of claim 369, wherein the treatment reduces the recurrence of cancer, wherein the recurrence is one or more of invasive ipsilateral breast tumor (IBTR) recurrence, local-regional invasive recurrence, and distant recurrence.

371. The method of claim 369, wherein the treatment reduces the spread of cancer, wherein the spread of cancer is an invasive contralateral breast cancer or an additional primary invasive cancer.

372. The method of any one of claims 274 to 371, wherein the treatment prevents death from cancer.

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