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; 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.

Subtype-Specific Survival of Young Women with Breast Cancer and Its Interaction with the Germline BRCA Status

“…gBRCAm is also associated with high chemosensitivity since it leads to a deficiency in DNA repair, so cytotoxic therapies inducing DNA damage might be especially effective [27]. Therefore, a positive value of gBRCAm on therapy response and survival in TNBC patients is being discussed [8,21,28,29]. Studies, yet not exclusively on young women, report higher response rates to several cytotoxic therapies in gBRCAm than gBRCAwt TNBC [28][29][30].…”

“…Some recent studies have also discussed a reverse association of the prognostic value of gBRCAm for TNBC and HR+ BC [10,11,21]. The negative effect of gBRCAm in HR+ tumors is still unclear but is speculated that it could be associated with younger age at the time of diagnosis [8].…”

“…Some more recent data that discuss the prognostic value of gBRCAm in the context of clinical subtypes indicate a favorable effect of gBRCAm for TNBC during the first 2 years after diagnosis [8]. Also, a reverse association of the prognostic value of gBRCAm with a potential negative effect for HR+ BC is being discussed, but the evidence is still very limited [10,11,21]. In Her2+ disease, young age and gBRCAm both do not seem to impact prognosis [3,4,11,22].…”