ArticleAnnals of surgical oncology2026
Germline BRCA1/2 Mutation Prevalence in Unselected ER-Low/HER2-Negative Breast Cancer.
Article in Annals of surgical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEstrogen receptor (ER)-low breast cancers, defined as tumors with 1-10% ER expression, exhibit clinicopathologic and molecular features, as well as chemotherapy responses, resembling triple-negative breast cancer (TNBC), leading to updated guidelines. However, current BRCA1/2 testing guidelines classify ER-low tumors alongside ER-strong-positive cancers, potentially overlooking mutation carriers. Thus, the purpose of this study was to determine whether BRCA1/2 genetic testing in patients with ER-low/HER2-negative breast cancer should be the same as those with TNBC. PATIENTS AND
methodsThis multicenter retrospective study included 271 unselected patients with ER-low/HER2-negative invasive breast cancer from four Korean institutions (2014-2022). BRCA1/2 genetic testing was performed via Sanger sequencing or next-generation sequencing. A previously published unselected TNBC cohort (n = 920) served as a comparator. Clinical and pathological characteristics and BRCA1/2 mutation prevalence were compared between groups.
resultsAmong 271 ER-low/HER2-negative patients, 41 (15.1%) carried pathogenic BRCA1/2 mutations (BRCA1: 11.8%, BRCA2: 3.3%), comparable to the TNBC cohort (13.2%; p = 0.404). BRCA1 predominance was observed, with the highest prevalence in patients ≤ 40 years (25.4% versus 20.0% in TNBC). Mutation carriers were younger (≤40 years: 41.5% versus 21.7%; p = 0.006), more often premenopausal (85.4% versus 50.0%; p < 0.001), and more frequently had a family history of breast/ovarian cancer (48.8% versus 16.1%; p < 0.001).
conclusionsER-low/HER2-negative breast cancers demonstrate BRCA1/2 mutation prevalence and features comparable to TNBC. Applying testing criteria based solely on ER expression may underdiagnose mutation carriers. These findings support expanding BRCA1/2 testing eligibility to include ER-low/HER2-negative tumors to ensure timely identification and access to targeted therapies.
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