Women with BRCA1 or 2 mutations have significantly reduced risk for ovarian, fallopian tube, and peritoneal cancers after salpingo-oophorectomy, according to an article in the July 12 issue of the Journal of the American Medical Association.

Women with a harmful mutation in the BRCA1 or BRCA2 gene have a high lifetime risk of ovarian cancer (range, 15 percent-54 percent), and mutations in either of these genes increase susceptibility to cancers of the ovary, fallopian tube, and peritoneum, according to background information in the article. Affected women are often advised to undergo preventive oophorectomy, but the effectiveness of this intervention has not been prospectively evaluated in a large group of patients.

Steven A. Narod, MD, of the Toronto-Sunnybrook Regional Cancer Center, Toronto, Ontario, and colleagues conducted a study to determine the absolute risks for developing ovarian, fallopian tube, and peritoneal cancers in a group of women carrying BRCA1 or BRCA2 mutations and estimated the risk reduction associated with salpingo-oophorectomy.

Women known to carry a BRCA1 or BRCA2 mutation were identified from an international registry. A total of 1,828 carriers at 1 of 32 centers in Canada, the United States, Europe, and Israel completed questionnaires at baseline and follow-up. Participants were observed from date of entry until diagnosis of ovarian, fallopian tube, or peritoneal cancer, death, or the date of the most recent follow-up.

After an average follow-up of 3.5 years, 50 new ovarian, fallopian tube, and peritoneal cancer cases were reported. Of the 1,828 women, 555 (30 percent) underwent preventive resection prior to study entry, 490 (27 percent) underwent the procedure after entering the study, and 783 (43 percent) did not undergo the procedure. Of the 50 cases, 32 were diagnosed in women with intact ovaries.

The estimated cumulative incidence of peritoneal cancer is 4.3 percent at 20 years after oophorectomy. The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80 percent. The researchers estimated the risk of ovarian cancer to be 62 percent for BRCA1 carriers and 18 percent for BRCA2 carriers in women up to age 75 with both ovaries intact.

"Women who carry a mutation in the BRCA1 gene are asked to consider prophylactic bilateral salpingo-oophorectomy at age 35 years or thereabouts, in order to reduce the risk of ovarian, fallopian tube, and breast cancer. Our observations support this recommendation. It may be reasonable to wait until a time closer to menopause to prevent ovarian and fallopian tube cancer in BRCA2 carriers but this delay will diminish the level of protection offered against breast cancer in this subgroup," the authors wrote.

"We estimate the magnitude of the risk reduction [from preventive removal of the ovaries and tubes] to be approximately 80 percent and the residual risk of 4 percent of peritoneal cancer is not sufficiently high to recommend against the procedure. It is important that both the fallopian tubes and ovaries be removed because either site may be the origin of cancer and both organs should be examined in fine detail to rule out the presence of microscopic disease," the researchers concluded.