Impact of Germline BRCA Mutation Status on Survival in Women with Metastatic Triple Negative Breast Cancer

Abstract

Purpose: To investigate the association between germline deleterious BRCA1 or BRCA2 mutations (gBRCA+) and overall survival (OS) for patients with metastatic triple negative breast cancer (mTNBC). Methods: An IRB approved prospective multisite registry enrolling stage I-IV TNBC patients from 2011-2018 was utilized. Demographics, treatments, genetic results, recurrence and survival were collected. OS was estimated according to the Kaplan-Meier method and compared between groups (gBRCA+and BRCA wild type, wt) by log-rank test. Cox regression model was used for univariate and multivariate analysis of factors associated with risk of death. Results: 100 patients with mTNBC were enrolled on the registry between 2011- 2018. For 100 patients, 20% (20/100) had de novo stage IV whereas 80% (80/100) had metastatic recurrence. 12% had gBRCA+ status; 72% were gBRCA wt type; and 16% had unknown gBRCA status. gBRCA+ patients were younger (49 vs. 57 years, p=0.02) but otherwise well matched to gBRCA wt including similar metastatic disease burden and prior treatments. No patients received a PARP inhibitor. With 31 months median follow-up, median overall survival was 21 months (95% CI [13-23] months) for all patients, 18 months (95% CI [15-27] months) for gBRCA wt patients and has not yet been reached for gBRCA+ patients (p=0.023). 3-year estimated OS is 63% in gBRCA+ versus 28% in gBRCA wt (p=0.02). On multivariate analysis, gBRCA+ was associated with reduced risk of death (HR=0.33; 95%CI [0.23-0.91], p=0.033). Conclusions: In patients with mTNBC gBRCA+ patients have a clinically significantly improved 3-year OS compared to gBRCA wt patients. Further research is needed to understand tumor and host biological reasons for this observation. As these patients are at risk for primary site progression and secondary breast and ovarian cancers, further research regarding the role of proactive surgical treatment in mTNBC with gBRCA mutation is warranted.