Prevalence of Pathogenic Germline BRCA1/2 Variants and Their Association with Clinical Characteristics in Patients with Epithelial Ovarian Cancer in a Rural Area of Japan.

The prevalence of germline BRCA1 or BRCA2 pathogenic variants (g BRCA1/2 -PV) in patients with primary epithelial ovarian cancer (OC) in a rural area of Japan and their association with clinical characteristics, including treatment response and survival outcome, were investigated. A total of 123 unbiased patients with OC were tested for g BRCA1 and g BRCA2 using next-generation sequencing-based targeted amplicon sequencing. Clinical characteristics of OC patients with and without g BRCA1/2 status were compared. The overall prevalence of g BRCA1/2 -PV was 15.4% (19 cases), with g BRCA2 -PV (10.5%, 13 cases) being more common than g BRCA1 -PV (4.9%, 6 cases). Among the observed g BRCA1/2 -PV, several novel variants were included, suggesting that g BRCA1/2 -PV unique to the local area exist. g BRCA1/2 -PV was significantly more prevalent in OC patients at an older age, with high-grade serous carcinoma, with advanced-stage tumors, and with a family history of breast cancer or hereditary breast and ovarian cancer syndrome (HBOC)-associated cancers. Patients with advanced-stage OC with g BRCA1/2 -PV showed a significantly lower recurrence rate and tended to have better progression-free and overall survival than those with wild-type g BRCA1/2 . Genetic testing for g BRCA1/2 status in all OC patients is useful not only for diagnosing HBOC in patients and their relatives to assess the risk of HBOC-associated cancers, but also to estimate therapy response and outcomes in patients.