Effect of BRCA mutation on prognosis in patients with ovarian cancer: A systematic review and meta-analysis.

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5066 Background: To investigate whether the germ-line mutations of BRCA 1 and 2 in patients with ovarian cancer are associated with disease outcome. Methods: A systematic search of the literature was performed using search terms related to BRCA, ovarian cancer and prognosis. Studies were considered eligible if they reported the outcome of ovarian cancer in patients with BRCA 1 and/or 2 mutations compared with patients with sporadic ovarian cancer or / and no BRCA mutation. Cohort and case-control designs were included. Pooled Hazard Ratios (HR) were estimated with fixed or random effects models, depending on between-studies heterogeneity. Results: Of 2,340 titles identified, 26 articles met the inclusion criteria. Of these, 6 studies were excluded from the analysis due to duplication of results (n=1) and lack of data to calculate HR (n=5). Patients with BRCA 1 or 2 mutations had better survival compared with control group both in cohort (HR: 0.58, 95% Confidence Interval (CI) 0.42-0.79, p-value 0.0005) and in case-control (HR: 0.65, 95% CI 0.45-0.93, p-value = 0.02) studies. When only patients with BRCA 1 mutation were analyzed, the survival benefit remained significant (HR: 0.67, 95% CI 0.53-0.85, p-value = 0.001). Furthermore, the differential survival benefit of the mutation groups was even more evident among patients with BRCA 2 mutation (HR: 0.43, 95% CI: 0.30-0.63, p-value < 0.0001). A direct comparison of patients with BRCA 1 vs. BRCA 2 mutations (4 studies) revealed a significantly better survival for BRCA 2 mutation carriers (HR: 0.53, 95% CI: 0.33-0.85, p-value = 0.009). Conclusions: Our results confirm the hypothesis that BRCA status is a prognostic factor in patients with ovarian cancer. Based on these results, the use of BRCA status as a stratifying factor in therapeutic ovarian cancer trials seems to be fully justifiable. The stronger association between survival and BRCA 2 mutation, compared with BRCA 1, suggests a different nature of the dysfunction of these 2 genes.