Association between BRCA mutational status and survival in patients with breast cancer: a systematic review and meta-analysis.

BACKGROUND: Studies evaluating role of BRCA mutations on the survival outcomes in breast cancer (BC) patients have given confounding results and hence, in this meta-analysis, we assessed the impact of BRCA mutations on survival in BC patients. METHODS: Studies comparing survival outcomes of BC patients having BRCA mutations against wildtype BRCA phenotype were retrieved from PubMed, EMBASE, and Cochrane Library. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCCS) were the outcomes. Hazard ratio (HR) with 95% confidence interval (CI) was used for analysis. Subgroup analysis was performed for survival based on triple negative breast cancer (TNBC) and follow-up durations. The meta-analysis was performed as per PRISMA guidelines. RESULTS: Altogether, 30 articles with 35,972 patients (mean age 45.6 years) were included. Patients with BRCA 1 mutation had significantly lower OS (HR [95% CI] 1.2 [1.08, 1.33]; P < 0.001), BRCA 2 mutation had significantly lower DFS (HR [95% CI] 1.35 [1.1, 1.67]; P = 0.0049) and BCSS (HR [95%CI] 1.46 [1.26, 1.7]; P < 0.0001), and TNBC patients with BRCA 1 mutation had significantly poor DFS (HR [95% CI] 1.65 [1.08, 2.54]; P = 0.0216). Based on follow-up duration, the OS in BRCA 1-mutated patients revealed significantly poorer outcomes in studies with ≤ 5 years (HR 1.48) and > 5 years (HR 1.14) of follow-up. In BRCA 2 -mutated patients, the OS was significantly poorer in studies with > 5 years of follow-up (HR 1.39, P < 0.05). CONCLUSION: BC patients with BRCA 1 or BRCA 2 mutations had poor survival outcomes and hence screening patients with BC for BRCA mutations might help in strategizing their treatment and improving their survival.