Risk-Reducing Salpingo-oophorectomy in Women with a BRCA1 or BRCA2 Mutation

Abstract & Commentary

Synopsis: Salpingo-oophorectomy in carriers of BRCA mutations can decrease the risk of breast cancer and BRCA-related gynecologic cancer.

Source: Kauff ND, et al. N Engl J Med. 2002;346: 1609-1615.

Kauff and colleagues conducted a prospective follow-up study of all women with BRCA1 or BRCA2 mutations identified during a 6-year period at their institution. They compared the effect of risk-reducing salpingo-oophorectomy with that of surveillance for ovarian cancer on the incidence of subsequent breast cancer and BRCA-related gynecologic cancers in women with BRCA mutations. A total of 170 women 35 years of age or older who had not undergone bilateral oophorectomy chose to undergo either surveillance for ovarian cancer or risk-reducing salpingo-oophorectomy. Follow-up involved an annual questionnaire telephone contact, and reviews of medical records. During a mean follow-up of 24.2 months, breast cancer was diagnosed in 3 of the 98 women who chose risk-reducing salpingo-oophorectomy, and peritoneal cancer was diagnosed in 1 woman in this group. Among the 72 women who chose surveillance, breast cancer was diagnosed in 8, ovarian cancer in 4, and peritoneal cancer in 1. The time to breast cancer or BRCA-related gynecologic cancer was longer in the salpingo-oophorectomy group, with a hazard ratio for subsequent breast cancer or BRCA-related gynecologic cancer of 0.25 (95% percent confidence interval, 0.08-0.74). Kauff et al concluded that salpingo-oophorectomy in carriers of BRCA mutations can decrease the risk of breast cancer and BRCA-related gynecologic cancer.

Comment by David M. Gershenson, MD

We have known for quite some time that women who are carriers of BRCA mutations have up to an 85% lifetime risk of invasive breast cancer and up to a 65% lifetime risk of epithelial ovarian cancer. Options for such women to date include screening—the efficacy of which is in question, particularly for ovarian cancer screening in high-risk women—chemoprevention (ie, oral contraceptives)—and prophylactic surgery. Based on retrospective study data, prophylactic bilateral salpingo-oophorectomy has been recommended for prevention of ovarian and fallopian tube cancer. However, some experts have questioned whether such surgery will prevent primary peritoneal cancer. This is one of the first, if not the first, prospective studies evaluating the role of prophylactic surgery in this high-risk cohort. Compared with the surveillance group, there were significantly fewer breast and gynecologic cancers in the prophylactic surgery group. Another study from The Prevention and Observation of Surgical End Points Study Group published in the same issue of the New England Journal of Medicine revealed similar findings.1 The complication rate in the Kauff study was acceptable at 4%. One of the major remaining questions is the role of concomitant hysterectomy and the benefit/risk ratio associated with this procedure. In the interim, female members of high-risk families should be seriously considering enrolling in a comprehensive program to undergo risk assessment and possible genetic counseling and genetic testing. In addition, we need more confirmatory prospective studies to gain important information regarding the relative efficacy of the available risk-reduction strategies.

Dr. Gershensen is Professor and Chairman Department of Gynecology, M.D. Anderson Cancer Center, Houston.

Reference

1. Kauff ND, et al. N Engl J Med. 2002;346:1616-1622.