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BACKGROUND: Whether outcomes of germline BRCA1/2 (gBRCA1/2)-associated breast cancer differ compared with sporadic tumors is controversial. We explored the impact of gBRCA1/2 pathogenic variant (PV) status beyond established prognostic features.METHODS: We conducted two retrospective, matched cohort studies comparing gBRCA1/2 PV carriers and non-carriers with HER2-negative, stage I-III breast cancer (Clinical Outcomes Quality Database [COQD] cohort: 185 carriers, 555 non-carriers; Young Women's Breast Cancer Study [YWS] cohort: 113 carriers, 226 non-carriers). Matching factors were age, stage, hormone receptor status and year of diagnosis. Clinicopathologic features, treatments and survival outcomes were compared between carriers and non-carriers.RESULTS: Most patients in COQD had stage I-II disease (87.2%) and more carriers than non-carriers had genetic testing before diagnosis (33% vs 5.6%, p < 0.001). In YWS, 22.7% of patients had stage III tumors and few were tested before diagnosis (14.8% of carriers vs 1.7% of non-carriers; p < 0.001). Carriers in COQD received chemotherapy more often than non-carriers (81.1 vs 67.0%, p < 0.001), including platinum (p = 0.010); the proportion was similar for carriers and non-carriers in YWS. After adjusting for chemotherapy, relapse-free survival was longer in carriers than non-carriers in COQD (adjusted hazard ratio 0.48 [95% CI = 0.26-0.87], p = 0.016), and a favorable trend was observed for other survival outcomes in both cohorts. Triple-negative tumors appeared to drive the differences.CONCLUSIONS: We observed a trend toward improved outcomes in gBRCA1/2 PV carriers compared to non-carriers. These findings suggest that carriers should not receive more aggressive treatment solely based on their germline mutation status. Prospective clinical trials in this population are warranted.