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

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.

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Breast Cancer Female
• Intervention / Treatment: Other: Translational study

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• United Kingdom
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 71 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

This is a non-interventional, translational study, using surgical tissue (collected as part of routine care) from older women (aged > 70 years at the time of diagnosis) with early (stage I-III), ER positive, HER2 negative BC who were treated curatively with primary surgery. Patients would not have had any prior treatment with (neo-) adjuvant chemotherapy but received an aromatase-inhibitor in the adjuvant setting.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of the molecular features with TTR (Defined as the time from diagnosis (initial biopsy) to local, regional, or distant tumour recurrence or death from breast cancer without prior notification of relapse.).	Exploratory	August 2023

Collaborators and Investigators

• Sponsor: Royal Marsden NHS Foundation Trust
• Collaborators: Institute of Cancer Research, United Kingdom; National Institute for Health Research, United Kingdom

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2022
• Primary Completion (Anticipated): August 31, 2023
• Study Completion (Anticipated): August 31, 2023

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Estimate): February 20, 2023

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: CCR5654

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No