Outcomes and treatment patterns in germline BRCA1/2 carriers from two matched cohort
Menée à partir de données de deux cohortes incluant respectivement 740 et 339 patientes atteintes d'un cancer du sein, cette étude analyse les traitements reçus et la survie associée, en fonction de la présence de mutations constitutionnelles BRCA
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.
JNCI Cancer Spectrum , résumé, 2026