Women with adverse mutations in the BRCA1 or BRCA2 gene are at an increased lifetime risk of ovarian cancer, and these mutations also increase vulnerability to cancers of the fallopian tube and peritoneum. Risk levels were examined in a prospective study based on data from an international registry comprising 32 centers in Canada, the United States, Europe, and Israel. The 1828 women identified as carrying a BRCA1 or BRCA2 mutation were followed up for a mean of 3.5 years. Participants had a mean age at entry of 47 years. Approximately three-fourths of the women carried a BRCA1 mutation and about one-fourth, a BRCA2 mutation; eight individuals carried both. Nearly one-third of women in the study (30.4%) had undergone bilateral salpingo-oophorectomy before entering the study, and another 38.5% had an oophorectomy during follow-up.
Fifty incident cancers were discovered during follow-up. Thirty-two of these cancers developed in women with intact ovaries. Eleven cancers were identified at the time of prophylactic oophorectomy, and 7 others after this procedure. The cumulative incidence of peritoneal cancer was estimated at 4.3% two decades after oophorectomy. The overall adjusted reduction in cancer risk associated with bilateral oophorectomy was 80%, with a multivariate hazard ratio of 0.2 and a 95% confidence interval of 0.07–0.58 (Fig. 1). The risk of ovarian, tubal, and primary peritoneal cancers in women with intact ovaries was highest for those 60–70 years of age who carried the BRCA1 mutation. Based on estimated incidence rates for women having both ovaries intact, the estimated penetrance of ovarian cancer was 62% up to age 75 years for carriers of the BRCA1 mutation, and 18% up to age 75 for those carrying the BRCA2 mutation.
The investigators conclude that the risk of ovarian, tubal, and peritoneal cancer is lowered by 80% for carriers of the BRCA1 or BRCA2 mutation who undergo prophylactic oophorectomy. The findings support prophylactic surgery as a very effective risk reduction measure. Both the ovaries and the fallopian tubes should be removed. The residual risk of peritoneal cancer is not high enough to recommend against prophylactic surgery.
Centre for Research in Women's Health, Toronto-Sunnybrook Regional Cancer Center, Toronto, Ontario; Pomerania Medical University, Szczecin, Poland; Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska; Norwegian Radium Hospital, Oslo, Norway; Department of Gynecology Ocology, University Health Network, University of Toronto; Department of Cancer Genetics, Departments of Medicine and Genetics, Epidemiology Research Unit, CHUM Hô-Dieu, University of Montreal, Montreal, Quebec; Chaim Sheba Medical Center, Tel Hashomer, Israel; Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, Quebec; BC Cancer Agency, Vancouver, British Columbia; Division of Serology, Medical University of Vienna and Private Trust for Breast Health, Vienna, Austria; Beth Israel Deaconess Medical Center, Boston, Massachusetts; Mayo Clinic College of Medicine, Rochester, Minnesota; Institute Marie Curie, Paris, France; London Regional Cancer Program, London, Ontario; Fox Chase Cancer Center, Philadelphia, Pennsylvania; Universita di Torino, Italy; Rambam Medical Center, Haifa, Israel; Ohio State University, Columbus, Cleveland Clinic Genomic Medicine Institute, Cleveland, Ohio; University of Chicago, Chicago, Illinois; Cancer Risk Program, San Francisco, California; Division of Gynecology Oncology, Cedars Sinai Medical Center, Los Angeles, California; and City of Hope Medical Center, Duarte, California