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

Frequency of germline mutations in BRCA1 and BRCA2 in ovarian cancer patients and their effect on treatment outcome., Ashour, Mohamed, and Shafik Hanan Ezzat , Cancer management and research, Volume 11, p.6275-6284, (2019)


Aim of work: Reporting the incidence and the variants of /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 genes. Responses to multiple lines of chemotherapy were assessed, as well as the effect of gene mutations on progression-free survival (PFS) and overall survival (OS).

Results: Pathogenic / mutations were found in 21.15% of the patients. mutations represented 68.2% of the total mutations. Two novel mutations were identified. Age at diagnosis was a strong predictor of the presence of a pathogenic mutation. Patients with a family history of cancer had a higher incidence of mutations (=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 (=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 (=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 (=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) (=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 and mutations in this patients cohort; two novel mutations were detected. BRCA status seemed to affect survival in ovarian cancer patients.