July 23, 2006 Women with mutations in the BRCA1 or BRCA2 genes can significantly reduce their risk of certain types of cancer by having their ovaries removed, according to a study in the July 12 issue of JAMA.
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 (abdominal lining), according to background information in the article. Women with this mutation are often advised to undergo preventive oophorectomy (surgical removal of the ovaries). The effectiveness of this intervention has not been prospectively evaluated in a large group of patients.
Steven A. Narod, M.D., 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 BRCA1 and BRCA2 mutation carriers and estimated the risk reduction associated with salpingo-oophorectomy (surgical removal of the ovaries and fallopian tubes). Women known to carry a BRCA1 or BRCA2 mutation were identified from an international registry between 1992 and 2003. 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 the date of study 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 in the group. Of the 1,828 women, 555 (30 percent) underwent preventive removal of the ovaries and tubes prior to study entry, 490 (27 percent) underwent the procedure after entering the study, and 783 (43 percent) did not undergo the procedure. There were 32 new cancers 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 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 write.
"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 conclude. (JAMA. 2006;296:185-192.)
Editor's Note: This work was supported by a grant from the Canadian Breast Cancer Research Alliance and from the National Institutes of Health.
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