Biology of Human Tumors Effects of BRCA1- and BRCA2-Related Mutations on Ovarian and Breast Cancer Survival: A Meta-analysis

Purpose: To estimate the effects of BRCA1 and BRCA2 mutations on ovarian cancer and breast cancer survival. Experimental Design: We searched PubMed and EMBASE for studies that evaluated the associations between BRCAmutations and ovarian or breast cancer survival. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS). Results: From 1,201 unique citations, we identified 27 articles that compared prognosis between BRCA mutation carriers and noncarriers in patients with ovarian or breast cancer. Fourteen studies examinedovarian cancer survival and13 studies examined breast cancer survival. For ovarian cancer, meta-analysis demonstrated that both BRCA1 and BRCA2mutation carriers had better OS (HR, 0.76; 95% CI, 0.70–0.83 for BRCA1 mutation carriers; HR, 0.58; 95% CI, 0.50–0.66 for BRCA2 mutation carriers) and PFS (HR, 0.65; 95% CI, 0.52–0.81 for BRCA1 mutation carriers; HR, 0.61; 95% CI, 0.47–0.80 for BRCA2 mutation carriers) than noncarriers, regardless of tumor stage, grade, or histologic subtype. Among patients with breast cancer, BRCA1mutation carriers hadworseOS (HR, 1.50; 95%CI, 1.11–2.04) thannoncarriers but were not significantly different from noncarriers in PFS. BRCA2 mutation was not associated with breast cancer prognosis. Conclusions: Our analyses suggest that BRCA mutations are robust predictors of outcomes in both ovarian and breast cancers and these mutations should be taken into account when devising appropriate therapeutic strategies. Clin Cancer Res; 21(1); 211–20. 2014 AACR.