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Cancer Incidence in a Population of Jewish Women at Risk of Ovarian Cancer

From the Centre for Research in Women’s Health, Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada; and Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, and Department of Obstetrics and Gynecology, University of California–Los Angeles School of Medicine, Los Angeles, CA.

Address reprint requests to S.A. Narod, MD, Centre for Research in Women’s Health, Sunnybrook and Women’s College Health Sciences Centre, 790 Bay St, Ste 750A, Toronto, Ontario M5G 1N8, Canada; email: alex.liede{at}swchsc.on.ca

PURPOSE: To evaluate the incidence and clinical characteristics of ovarian and other cancers in a cohort of women at risk of developing ovarian cancer.

PATIENTS AND METHODS: The Gilda Radner Ovarian Cancer Detection Program in Los Angeles, CA, was established in 1991 to study the efficacy of screening in the early detection of ovarian cancer. We present findings from a historical cohort of 290 Jewish women who were offered BRCA testing for three common founder mutations (BRCA1 185delAG and 5382insC and BRCA2 6174delT).

RESULTS: In 10 years, 17 cancers were observed (1,111 per 100,000 per year), including six breast and eight ovarian or related cancers. A high proportion of cancers of peritoneal origin was observed. The majority (86%) of women with incident breast or ovarian/peritoneal cancer carried a mutation in the BRCA1 gene. The overall cancer incidence among carriers of mutations in the BRCA1 gene was estimated to be 5,450 per 100,000 per year, corresponding to a cumulative incidence of 47.5% at 10 years. In contrast, the cumulative incidence of cancer among noncarriers was 2.5% (P < 10^-8). After adjustment for sampling, the risks to BRCA1 mutation carriers at 10 years were estimated to be 21% for ovarian/peritoneal/tubal cancer, 16% for breast cancer, and 36% for all cancers.

CONCLUSION: The excess risk of breast and ovarian cancer in Jewish women with a family history of ovarian cancer is largely attributable to mutations in BRCA1. Intensive surveillance by use of CA-125 and ultrasound does not seem to be an effective means of diagnosing early-stage ovarian cancer in this high-risk cohort.

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