Frequency of germline mutations in BRCA1 and BRCA2 in ovarian cancer patients and their effect on treatment outcome

AIM OF WORK: Reporting the incidence and the variants of BRCA1/2 mutations in ovarian cancer patients exploring their effects on the treatment outcomes. PATIENTS AND METHODS: In total, 104 patients with epithelial ovarian cancer were prospectively recruited to the study. Analysis consisted of the sequencing of all the translated exons and immediately adjacent intronic regions of the BRCA1/2 genes. Responses to multiple lines of chemotherapy were assessed, as well as the effect of BRCA gene mutations on progression-free survival (PFS) and overall survival (OS). RESULTS: Pathogenic BRCA1/2 mutations were found in 21.15% of the patients. BRCA1 mutations represented 68.2% of the total mutations. Two novel BRCA1 mutations were identified. Age at diagnosis was a strong predictor of the presence of a pathogenic BRCA1/2 mutation. Patients with a family history of cancer had a higher incidence of BRCA mutations (P=0.005). As high as 72% of the patients with BRCA mutations were diagnosed at advanced stage. High-grade serous tumors have a higher incidence of pathogenic mutation (P=0.07). Response to neoadjuvant chemotherapy was high (93.9%). All patients underwent surgery which was optimal in 73.1% of the patients. As high as 85.6% of the patients received adjuvant chemotherapy. Relapse rate was 45.2%. Visceral metastasis was more often in BRCA carriers (P=0.01). Patients carrying pathogenic BRCA1/2 mutations had a longer median PFS of 42.43 months (95% CI 32.04–52.83) compared to 22.24 months (95% CI 14.83–29.58) for non-carriers (P=0.08). OS was 64.32 months (95% CI 38.09–90.06) for BRCA mutation patients versus 56.63 months (95% CI 50.05–63.21) (P=0.04) for non-carriers. In multivariate analysis, early stage at diagnosis and optimal debulking were the only independent predictors of better PFS and OS. CONCLUSION: We documented a number of pathogenic BRCA1 and 2 mutations in this patients cohort; two novel mutations were detected. BRCA status seemed to affect survival in ovarian cancer patients.