Germline BRCA1/2 Mutation Prevalence in Unselected ER-Low/HER2-Negative Breast Cancer.

Area of Science:

• Oncology
• Genetics
• Breast Cancer Research

Background:

• Estrogen receptor (ER)-low breast cancers share characteristics with triple-negative breast cancer (TNBC).
• Current BRCA1/2 genetic testing guidelines may not adequately identify mutation carriers within the ER-low population.
• Updated guidelines are needed to address the specific needs of ER-low breast cancer patients.

Purpose of the Study:

• To compare BRCA1/2 mutation prevalence in ER-low/HER2-negative breast cancer with TNBC.
• To determine if ER-low/HER2-negative breast cancer patients warrant the same BRCA1/2 genetic testing criteria as TNBC patients.

Main Methods:

• A multicenter retrospective study of 271 patients with ER-low/HER2-negative invasive breast cancer.
• BRCA1/2 genetic testing performed using Sanger sequencing or next-generation sequencing.
• Comparison with a cohort of 920 unselected TNBC patients.

Main Results:

• Pathogenic BRCA1/2 mutations were found in 15.1% of ER-low/HER2-negative patients, comparable to 13.2% in TNBC.
• BRCA1 mutations were predominant, especially in patients ≤40 years (25.4%).
• Mutation carriers were younger, more often premenopausal, and had a higher frequency of family history of breast/ovarian cancer.

Conclusions:

• ER-low/HER2-negative breast cancers exhibit BRCA1/2 mutation prevalence similar to TNBC.
• Current testing criteria based solely on ER expression may lead to underdiagnosis of mutation carriers.
• Expanding BRCA1/2 testing eligibility to ER-low/HER2-negative tumors is supported to ensure timely identification and treatment access.