Semi-Quantitative Evaluation of BRCA1 Protein in Breast Tumors Using Anti-BRCA1 Antibodies: Clinical Implications

Aggressive breast cancer subtypes, such as triple-negative breast cancer (TNBC) and tumors in BRCA1 germline mutation carriers, present significant clinical challenges. The role of BRCA1 protein expression, assessed via immunohistochemistry (IHC), in defining the biology of these high-risk tumors remains to be fully elucidated. We performed a semi-quantitative IHC analysis of BRCA1 protein expression in a targeted cohort of 100 invasive breast carcinomas, enriched for TNBC (88%) and BRCA1 mutation carriers (34%). A validated monoclonal antibody and a composite scoring system (0-9) were employed, with an optimal cut-off defined by ROC analysis. Associations with clinicopathological parameters and p16 expression were evaluated. Low BRCA1 expression was strongly associated with an aggressive phenotype, including invasive ductal histology, hormone receptor negativity, and the TNBC subtype (all p < 0.001). Tumors with BRCA1 loss exhibited a more pro-tumorigenic microenvironment, characterized by higher rates of necrosis (p = 0.014) and denser mononuclear infiltrates (p = 0.019). A significant inverse correlation with p16 overexpression was identified (p = 0.030). Our findings demonstrate that BRCA1 protein loss delineates a distinct aggressive tumor biology within high-risk breast cancers. We emphasize that BRCA1 IHC is a complementary biomarker and cannot supplant germline genetic testing for clinical decision-making regarding targeted therapies.