Effect of BRCA mutations on the length of survival in epithelial ovarian tumors

Purpose: To study the role of BRCA mutations in ovarian cancer survival. Patients and Methods: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide casecontrol study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174deIT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. Results: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v 37.8 months; 3-year survival, 65.8% v 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. Conclusion: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.