Survival outcomes of metastatic breast cancer patients by germline BRCA1/2 status in a large multicenter real-world database.

ABSTRACT

The outcomes and best treatment strategies for germline BRCA1/2 mutation (gBRCAm) carriers with metastatic breast cancer (MBC) remain uncertain. We compared the overall survival and the first line progression free survival (PFS1) of patients with a gBRCAm identified at initiation of first-line treatment with those of BRCA wild-type (WT) and not-tested (NT) individuals in the ESME real-world database of MBC patients between 2008 and 2016 (NCT03275311). Among the 20 624 eligible patients, 325 had a gBRCAm, 1138 were WT and 19 161 NT. Compared with WT, gBRCAm carriers were younger, and had more aggressive diseases. At a median follow-up of 50.5 months, median OS was 30.6 (95%CI 21.9-34.3), 35.8 (95%CI 32.2-37.8) and 39.3 months (95% CI 38.3-40.3) in the gBRCAm, WT and NT subgroups, respectively. Median PFS1 was 7.9 (95%CI 6.6-9.3), 7.8 (95%CI 7.3-8.5) and 9.7 months (95%CI, 9.5-10.0). In the multivariable analysis conducted in the whole cohort, gBRCAm status had however no independent prognostic impact on OS and PFS1. Though, in the triple-negative subgroup, gBRCAm patients had better OS and PFS1 (HR vs WT = 0.76; 95%CI 0.60-0.97; P = .027 and 0.69; 95% CI 0.55-0.86; P = .001, respectively). In contrast, in patients with HR+/HER2 negative cancers, PFS1 appeared significantly and OS non significantly lower for gBRCAm carriers (PFS1 HR vs WT = 1.23; 95%CI 1.03-1.46; P = .024; OSHR = 1.22, 95% CI 0.97-1.52, P = .089). In conclusion, gBRCA1/2 status appears to have divergent survival effects in MBC according to IHC subtype.