Abstract P3-03-05: Association between BRCA1 and BRCA2 mutations and survival in breast cancer patients according to molecular subtype

Cancer Research(2018)

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摘要
Background: Germline mutations in BRCA1 / BRCA2 genes increase the risk of breast and ovarian cancers. In ovarian cancer patients (pts) treated with platinum, BRCA1, and especially BRCA2, carriers have better survival than non-carriers. In breast cancer pts, BRCA1 carriers have higher response rate to neoadjuvant chemotherapy, however the benefit on survival remains unclear. Patients and Methods: A cohort study was conducted in France and Switzerland and consisted in 860 pts diagnosed with early breast cancer who underwent genetic screening for BRCA1/BRCA2 germline mutations and who received neo(adjuvant) chemotherapy. Disease-free survival (DFS) and Breast-cancer specific survival (BCSS) were analyzed according to BRCA1/BRCA2 mutations and breast cancer subtype (triple negative breast cancers (TNBC) vs non-TNBC). Results: One hundred and forty-three pts carried BRCA1 mutation; 88 had BRCA2 mutation; and 629 were non-carriers. Median age at diagnosis was 39 years; median follow-up was 4.8 years. Two hundred and fifty-three pts had TNBC ( 94 BRCA1 , 14 BRCA2 and 145 non-carriers), and 607 had non-TNBC (49 BRCA1 , 74 BRCA2 and 484 non-carriers). Among TNBC pts, BRCA2 mutations were associated with higher 5-years DFS (100% vs 71% for non-carriers and 80% for BRCA1 carriers; log-rank p =0.040), and BCSS (100% vs 78% for non-carriers and 92% for BRCA1 carriers; log-rank p =0.011). BRCA1 mutations were associated with higher 5-years DFS compared to non-carriers, but the association did not reach statistical significance (HR adjusted on nodal status=0.64; 95%CI 0.36-1.16, Wald test p =0.14). BRCA1 mutations were associated with an improved 5-years BCSS compared to non-carriers (HR adjusted on nodal status=0.38; 95%CI 0.16-0.87, Wald test p =0.022). In non-TNBC patients, BRCA1 or BRCA2 mutations were not associated with higher 5-years DFS (79% for BRCA1 , 79% for BRCA2 carriers, and 80% for non-carriers; log-rank p =0.88) nor BCSS (94%, 92%, and 94% respectively; log-rank p =0.79). Conclusions: Among pts with TNBC, having BRCA germline mutation was associated with improved survival. In our cohort of TNBC pts, BRCA2 carriers did not present breast cancer relapse. Citation Format: Tredan O, De Talhouet S, Peron J, Friedlaender A, Vuilleumier A, Viassolo V, Ayme A, Chappuis PO, Buisson A, Bonadona V, Bodmer A, Labidi-Galy SI. Association between BRCA1 and BRCA2 mutations and survival in breast cancer patients according to molecular subtype [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-03-05.
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