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Effect of BRCA Mutations on the Length of Survival in Epithelial Ovarian Tumors

From the Department of Gynecology, Haemek Medical Center, Afula; Department of Clinical Epidemiology and Oncogenetic and Gynecology Oncology Units, Sheba Medical Center, Tel Hashomer; Department of Gynecology, Rambam Medical Center, Haifa; Department of Gynecology, Shaare Zedek Medical Center, Jerusalem; Department of Gynecology, Sapir Medical Center, Kfar Saba; Department of Gynecology, Rabin Medical Center, Petah Tikvah; Department of Gynecology, E. Wolfson Medical Center, Holon; Department of Gynecology, Soroka Medical Center, Beer Sheva; and Stanley Steyer Institute, Tel Aviv University Medical School, and Ariel College, Tel Aviv, Israel; and Laboratory of Population Genetics, National Cancer Institute, Bethesda, MD.

Address reprint requests to Angela Chetrit, MSc Unit of Cancer Epidemiology, Gertner Institute, Chaim Sheba Medical Center, RamatGan, Israel; email: angelac{at}gertner.health.gov.il

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 case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) 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.

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