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

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; OS:HR = 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.