Biological Characteristics of Older Women (> 70 Years) With ER Positive, HER2 Negative Early Breast Cancer

Study Overview
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Brief Summary
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This study is investigating the biological characteristics of early oestrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC) in older woman (aged > 70 years) who were treated with adjuvant endocrine treatment (ET). It will use surgical tissue previously collected as part of routine care from patients aged 70 years or older at diagnosis with ER positive, HER2 negative stage I-III BC treated The Royal Marsden NHS Foundation Trust (RMH). The overarching aim of this study is to define the biological characteristics of early BC in older women in terms of tumour microenvironment (TME), molecular and genomic features. This analysis will include assessment of tumour infiltrating lymphocytes (TILs), and gene expression profiling with NanoString using the Breast Cancer 360 (BC360TM) assay measuring ribonucleic acid (RNA) expression signatures of genes involved in proliferation, endothelial, angiogenesis, cytotoxicity, stroma, inflammatory chemokines, and apoptosis. This analysis will examine various biological pathways, aiming to inform suitability for certain treatments including cyclin-dependent kinase inhibitors (CDKi), chemotherapy, immunotherapy, or targeted treatments such as phosphoinositide 3-kinases (PI3K) inhibitors, or deoxyribonucleic acid (DNA) damage response.

Official Title
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Biological Characteristics of Older Women (> 70 Years) With Oestrogen-receptor (ER) Positive, Human Epidermal Growth Factor 2 (HER2) Negative Early Breast Cancer: Definition of Molecular and Genomic Features.

Conditions
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Breast Cancer Female

Intervention / Treatment
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* Other: Translational study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-menopausal women aged >70 years at the time of diagnosis of invasive breast cancer. ER positive (Allred score >5/8), HER2 negative early invasive BC. Stage I-III BC. Surgical tissue available. No pre-surgical systemic therapy (i.e., no pre-operative ET or chemotherapy). Planned adjuvant ET with an aromatase-inhibitor. No adjuvant chemotherapy. Surgery was performed between 1st January 2014 and 31st December 2016. Exclusion Criteria: Pre- or perimenopausal. ER negative or HER2-positive BC. Multifocal cancer where not all of foci ER positive HER2 negative Bilateral breast cancer. Stage IV breast cancer. Benign histology or DCIS. Pre-surgical treatment. Prior chemotherapy for BC.

Ages Eligible for Study
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Minimum Age: 71 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Translational study|Non-interventional, translational study|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of TILs percentage | assessed via immunohistochemistry | August 2023 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene expression profile patterns across the cohort. | assessed via genomic profiling | August 2023 | 
| Relationship between PAM50, Ki67 (<10% low, ≥ 10% high), PD-L1, modified AIR-CIS | assessed with advanced machine learning methods | August 2023 |