Methods and compositions for evaluating breast cancer prognosis

Abstract

Methods and compositions for evaluating the prognosis of a breast cancer patient, particularly an early-stage breast cancer patient, are provided. The methods of the invention comprise detecting expression of at least one, more particularly at least two, biomarker(s) in a body sample, wherein overexpression of the biomarker or a combination of biomarkers is indicative of breast cancer prognosis. In some embodiments, the body sample is a breast tissue sample, particularly a primary breast tumor sample. The biomarkers of the invention are proteins and / or genes whose overexpression is indicative of either a good or bad cancer prognosis. Biomarkers of interest include proteins and genes involved in cell cycle regulation, DNA replication, transcription, signal transduction, cell proliferation, invasion, proteolysis, or metastasis. In some aspects of the invention, overexpression of a biomarker of interest is detected at the protein level using biomarker-specific antibodies or at the nucleic acid level using nucleic acid hybridization techniques.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 612,073, filed Sep. 22, 2004, and U.S. Provisional Application Ser. No. 60 / 611,965, filed Sep. 22, 2004, both of which are incorporated herein by reference in their entirety.FIELD OF THE INVENTION [0002] The present invention relates to methods and compositions for evaluating the prognosis of a patient afflicted with breast cancer, particularly early-stage breast cancer. BACKGROUND OF THE INVENTION [0003] Breast cancer is the second most common cancer among American women, less frequent only than skin cancer. An American woman has a one in eight chance of developing breast cancer during her lifetime, and the American Cancer Society estimates that more than 250,000 new cases of breast cancer will be reported in the U.S. this year. Breast cancer is the second leading cause of cancer deaths in women, with more than 40,000 Americans expected to die from the dise...

AI Technical Summary

Benefits of technology

[0009] Methods and compositions for evaluating the prognosis of a cancer patient, particularly a breast cancer patient, are provided. The methods comprise detecting expression of at least one, more particularly at least two, biomarker(s) in a body sample, wherein the overexpression of a biomarker or combination of biomarkers is indicative of cancer prognosis. Overexpression of the biomarker or combination of biomarkers of the invention is indicative of either a good prognosis (i.e., disease-free survival) or a bad prognosis (i.e., cancer recurrence, metastasis, or death from the underlying cancer). Thus, the present method permits the differentiation of breast cancer patients with a good prognosis from those patients with a bad prognosis. The methods disclosed herein can be used in combination with assessment of conventional clinical factors (e.g., tumor size, tumor grade, lymph node status, and family history) and / or analysis of the expression level of molecular markers, such as Her2 / neu, Ki67, p53, and estrogen and progesterone hormone receptors. In this manner, the methods of the invention permit a more accurate evaluation of breast cancer prognosis.

[0010] The biomarkers of the invention are proteins and / or genes whose overexpression is indicative of cancer prognosis, including those biomarkers involved in cell cycle regulation, DNA replication, transcription, signal transduction, cell proliferation, invasion, or metastasis. The detection of overexpression of the biomarker genes or proteins of the invention permits the evaluation of cancer prognosis and facilitates the separation of breast cancer patients into good and bad prognosis risk groups for the purposes of, for example, treatment selection.

Problems solved by technology

Despite these advances, approximately 20% of women diagnosed with early-stage breast cancer have a poor ten-year outcome and will suffer disease recurrence, metastasis, or death within this time period.

The current clinical consensus is that at least some early-stage, node-negative breast cancer patients should receive adjuvant chemotherapy, but presently there are no widely used assays to risk stratify patients for more aggressive treatment.

Since the majority of these early-stage cancer patients enjoy long-term survival following surgery and / or radiation therapy without further treatment, it is likely inappropriate to recommend aggressive adjuvant therapy for all of these patients, particularly in light of the significant side effects associated with cancer chemotherapeutics.

Overexpression of human epidermal growth factor receptor 2 (HER-2 / neu), a transmembrane tyrosine kinase receptor protein, has been correlated with poor breast cancer prognosis.

Furthermore, approximately one-third of breast cancers have mutations in the tumor suppressor gene p53, and these mutations have been associated with increased disease aggressiveness and poor prognostic outcome.

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