Outcomes and treatment patterns in germline BRCA1/2 carriers from two matched cohort
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ID: 315007
2026
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Abstract
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.
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| Authors | Stefania Morganti, Se Eun Kim, Qingchun Jin, Jaeyoon Cha, Jacqueline E Zeigler, Alexandra Bili Newman, Gregory J. Kirkner, Craig Snow, Yue Zheng, Julie Vincuilla, Tonia Parker, Ryan M. Buehler, Brittany L Bychkovsky, Kate E. Dibble, Tal Sella, Kathryn J Ruddy, Shoshana M Rosenberg, Laura C. Collins, Jeffrey Peppercorn, Lidia Schapira, Virginia F. Borges, Yaileen D Guzman-Arocho, Steven E. Come, Ellen Warner, Philip D. Poorvu, Matteo Lambertini, G Curigliano, Melissa E. Hughes, Elizabeth A Mittendorf, Tari A King, Nancy U Lin, Judy E Garber, Nabihah Tayob, S M Tolaney, Ann H Partridge, Filipa Lynce |
| Journal | jnci cancer spectrum |
| Year | 2026 |
| DOI |
10.1093/jncics/pkag055
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| URL | |
| Keywords | Keywords not found |
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