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

• Published in: International journal of cancer 2023-03, Vol.152 (5), p.921-931
• Main Authors: Mailliez, Audrey, D'Hondt, Veronique, Lusque, Amelie, Caron, Olivier, Cabel, Luc, Goncalves, Anthony, Debled, Marc, Gladieff, Laurence, Ferrero, Jean‐Marc, Petit, Thierry, Mouret‐Reynier, Marie Ange, Eymard, Jean‐Christophe, Levy, Christelle, Uwer, Lionel, Leheurteur, Marianne, Desmoulins, Isabelle, Bachelot, Thomas, Frenel, Jean‐Sebastien, Motte Rouge, Thibault, Simon, Gaëtane, Jacot, William, Delaloge, Suzette
• Format: Article
• Language: English
• Subjects: BRCA1 protein; BRCA1 Protein - genetics; Breast cancer; Breast Neoplasms - pathology; Cancer; Cancer Epidemiology; ErbB-2 protein; Female; germline BRCA mutation; Humans; Life Sciences; Medical research; Metastases; Metastasis; metastatic breast cancer; Prognosis; Progression-Free Survival; real world; Survival
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.34304

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. What's new? Despite the recent approval of novel therapeutics for germline BRCA1/2‐mutated metastatic breast cancer, data regarding outcomes and optimal treatment strategies are lacking. This study assessed the impact of germline BRCA mutations on metastatic breast cancer survival using data from a cohort of patients treated in an era predating PARP inhibitors. Although germline BRCA mutation had no independent prognostic impact on survival, divergent prognostic effects according to tumor subtype were observed. These effects were pronounced among germline mutation carriers with luminal breast cancer, who experienced worse progression‐free survival. The observations highlight the importance of deciphering BRCA status early in clinical care.