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Effect of BRCA1/2 Mutations on Long-Term Survival of Patients With Invasive Ovarian Cancer: The National Israeli Study of Ovarian Cancer

Angela Chetrit, Galit Hirsh-Yechezkel, Yehuda Ben-David, Flora Lubin, Eitan Friedman, Siegal Sadetzki

From the Cancer and Radiation Epidemiology Unit, Gertner Institute; Department of Oncogenetics, Chaim Sheba Medical Center, Tel Hashomer; Department of Gynecology, Haemek Medical Center, Afula; and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Corresponding author: Angela Chetrit, MSc, Gertner Institute, Chaim Sheba Medical Center, Hashomer, 52621, Israel; e-mail: angelac{at}gertner.health.gov.il

Purpose To evaluate the long-term survival of ovarian cancer (OvC) patients in total and by BRCA1/2 mutation status.

Patients and Methods In a nationwide case-control study on OvC conducted in Israel between 1994 and 1999, 779 Jewish women with epithelial invasive OvC were tested for the three Ashkenazi Jewish founder mutations in BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT) genes and followed for survival up to 2003. Of the 605 women of Ashkenazi origin, 213 (35.2%) carried a mutation in the BRCA1/2 genes. Clinical characteristics were abstracted from the patients' medical records. The Kaplan-Meier method, log-rank tests, and stepwise Cox regression model were used for survival analyses.

Results The 5-year survival rate for the entire group was 39%. Median survival for carriers was significantly longer than for noncarriers (53.7 v 37.9 months, respectively; P = .002). This differential survival was pronounced among women diagnosed at stages III to IV (5-year survival rates of 38.1% and 24.5% for carriers and noncarriers, respectively; P < .001) and for women with poor grade (45.4% v 31.5%, for carriers and noncarriers, respectively; P < .001). These results remained significant after controlling for age at diagnosis, grade, and morphology. This benefit in prognosis was seen for both BRCA1 and BRCA2 carriers compared with noncarriers. During the study period (median follow-up, 6.2 years), being a BRCA1/2 mutation carrier decreased the mortality rate by 28%.

Conclusion This study confirms that, among Ashkenazi OvC patients, BRCA1/2 mutations are associated with improved long-term survival. This may be due to distinct clinical behavior and/or to a better response to chemotherapy.

Supported in part by Grant No. CA 61126-03 from the National Cancer Institute (National Institutes of Health, Bethesda, MD), and a grant from the Israel Cancer Association.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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