RNA Expression Profiling for Invasive Lobular Breast Cancer Subtyping

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Solution Overview

Problem

Current breast cancer treatment decisions often overlook the unique characteristics of invasive lobular carcinomas (ILCs), leading to inadequate responses to chemotherapy and unclear clinical outcomes, as existing methods primarily focus on invasive ductal carcinomas (IDCs), necessitating a more precise typing method for ILCs to identify aggressive subtypes and tailor treatments.

Innovation Solution

A method involving RNA expression profiling using specific genes like GIMAP6 and P2RY14 to subtype invasive lobular breast cancer, comparing patient samples to reference samples, allowing for the classification into Immune Related (IR) or Hormone Response (HR) subtypes, guiding targeted therapies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If gene expression-based molecular subtypes are used to describe breast cancers, then treatment precision is improved, but these subtypes were mainly defined based on IDCs leaving ILC largely uncharacterized

Engineering Contradiction:
Improvetyping precisionVSAvoidsubtype coverage
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent develops a specialized gene expression profile specifically tailored for ILC subtyping, rather than applying general breast cancer subtyping methods. This local adaptation allows the typing method to be optimized for the specific molecular characteristics of ILC, improving both precision and applicability to this particular cancer subtype.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent identifies and utilizes specific gene expression parameters (including GIMAP6 and P2RY14) that are differentially expressed in ILC subtypes. By changing the focus from general breast cancer markers to ILC-specific gene expression parameters, the method achieves accurate subtyping for this previously undercharacterized cancer type.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If treatment decisions are based on large breast cancer trials, then statistical power is improved, but ILCs are only a minor subgroup so conclusions may not apply to ILC

Engineering Contradiction:
Improveevidence robustnessVSAvoidsubtype applicability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the breast cancer population by developing distinct molecular subtypes specifically for ILC. This segmentation allows for ILC-specific treatment recommendations rather than applying general breast cancer trial conclusions, improving the applicability of treatment decisions to this specific subgroup while maintaining statistical rigor through dedicated molecular characterization.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces molecular subtyping as an intermediary layer between general breast cancer trial data and ILC-specific treatment decisions. By classifying ILC into distinct molecular subtypes, the method bridges the gap between large-scale trial evidence and personalized ILC treatment, allowing for more accurate prediction of treatment response in this specific patient population.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If ILCs are treated as a homogeneous group, then treatment simplicity is improved, but ILCs have unique biology and distinct patterns of distant metastases indicating heterogeneity

Engineering Contradiction:
Improvetreatment simplicityVSAvoidbiological heterogeneity
Core Design Contradiction:
Ease of operationVSLoss of information

Solution Approach 1:

The patent segments ILC into distinct molecular subtypes based on gene expression profiles, revealing the biological heterogeneity within this cancer type. This segmentation allows for more precise treatment strategies tailored to specific ILC subtypes while maintaining a systematic approach that builds upon the initial simplicity of treating ILC as a single entity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies partial subtyping by focusing on key gene expression markers that capture the most clinically relevant heterogeneity in ILC. Rather than attempting to classify all possible biological variations, the method identifies and utilizes a subset of genes (including GIMAP6 and P2RY14) that provide sufficient discriminatory power for clinically meaningful subtyping, balancing complexity with practical utility.

Inventive Principle:
Principle #16Partial or excessive action

Data Source

PatentEP3271479B1Methods and means for subtyping invasive lobular breast cancer
Publication Date: 2019.07.17 AGENDIA NV
  • EP3271479B1 patent drawingFigure 1A~1B
  • EP3271479B1 patent drawingFigure 2
  • EP3271479B1 patent drawingFigure 3

AI summary

The invention relates to methods and means of typing a sample from a breast cancer patient, preferably an invasive lobular breast cancer patient. The invention further relates to methods of assigning treatment to a patient suffering from invasive lobular breast cancer, and to methods of treating a patient suffering from invasive lobular breast cancer.