Women who are at high risk of ovarian cancer because they carry mutated BRCA1 and BRCA2 genes can reduce by about 80 percent their risk of developing this and other cancers of the reproductive organs by having preventive surgery to remove their ovaries and fallopian tubes, according to the largest prospective study yet done on the issue.
Journal of the American Medical Association, July 12, 2006 (see the journal abstract)
( JAMA. 2006 Jul 12;296(2):185-92)
Women who carry mutations in their BRCA1 and BRCA2 genes are at high risk of ovarian cancer, as well as cancer of the fallopian tubes and peritoneum (lining of the abdomen). These women are often advised to reduce their risk by undergoing preventive surgery to remove the ovaries and fallopian tubes. This procedure is called a salpingo-oophorectomy.
Until now, however, no large prospective study had been done to evaluate how effective this procedure actually was in preventing cancer. In a prospective study, researchers follow patients forward in time to see what happens to them. This study design is considered more reliable than a retrospective study, in which researchers look back at what happened to patients in the past.
The prospective study described here involved 1,828 women with BRCA1 or BRCA2 mutations. Researchers used an international registry to identify the women, whose average age when they enrolled in the study was 47. About 75 percent of the women carried a BRCA1 mutation, about 24 percent had a BRCA2 mutation, and fewer than one percent had mutations in both genes.
At the time they entered the study, 555 women (30.4 percent) had already undergone preventive surgery to remove their ovaries and fallopian tubes. Of those who had not, 490 (38.5 percent) underwent the procedure during the study period. A total of 783 women did not have preventive surgery during the course of the study.
The women completed initial and follow-up questionnaires that asked about childbearing, surgery, mammograms and other cancer-screening practices, and use of birth control pills and hormone therapy.
Researchers followed the women for an average of 3.5 years, and used statistical techniques to determine whether preventive surgery reduced the risk of cancer during that time. The study’s senior author is Steven A. Narod, M.D., of the Center for Research in Women’s Health in Toronto, Canada.
Of the 783 women with intact ovaries - that is, who had not had preventive surgery to remove their ovaries - 32 (4.1 percent) were diagnosed with cancer of the ovaries, fallopian tubes, or peritoneum during the follow-up period. Of these 32 cases, 29 occurred in women with BRCA1 mutations, and three in women with BRCA2 mutations.
Of the 490 women who had preventive surgery during the study’s follow-up period, 11 (2.2 percent) were unexpectedly found to have cancer when the surgery was performed. Of these 11 cases, nine occurred in women with BRCA1 mutations and two in women with BRCA2 mutations.
Among the 1,045 women who had preventive surgery either before or during study participation, seven (0.7 percent) were diagnosed with cancer of the peritoneum during the follow-up period. Six of these women had a BRCA1 mutation and one had a BRCA2 mutation.
On the basis of these findings, the researchers estimated that
- women with intact ovaries who carry a BRCA1 mutation have a 62 percent risk of developing ovarian cancer by age 75.
- women with intact ovaries who carry a BRCA2 mutation have an 18 percent risk of developing ovarian cancer by age 75.
- preventive surgery to remove the ovaries and fallopian tubes reduces the risk of a related cancer by 80 percent in women who carry a BRCA1 or BRCA2 mutation. (There isn’t a 100 percent reduction because cancer originating in these organs might have begun to spread prior to their removal.)
- women who undergo preventive surgery retain a four percent risk of developing cancer of the peritoneum.
“Our study supports the recommendation for [preventive] oophorectomy as a highly effective means of reducing the risk of ovarian and fallopian tube cancers in BRCA1 and BRCA2 carriers,” Narod and his colleagues write. The fact that a small risk of developing peritoneal cancer remains after surgery is not enough to recommend against the procedure, the researchers add.
This study’s findings confirm that preventive surgery to remove the ovaries and fallopian tubes is the standard of care for women with BRCA1 or BRCA2 mutations who have completed childbearing, says Mark H. Greene, M.D., of the National Cancer Institute’s Division of Cancer Epidemiology and Genetics.
“This excellent article may help to make that fact more widely known in the general medical community,” he says.
The results also suggest that peritoneal cancer after risk-reducing surgery is less common than many cancer genetics specialists had thought, adds Greene. “Most women who have [preventive surgery] do not develop peritoneal cancer. This finding is good news.”
Despite the fact that this is the largest study of this question ever done, the researchers’ estimate that preventive surgery reduces the risk of cancer by 80 percent in women who carry a BRCA1 or BRCA2 mutation is based on a relatively small number of cancer cases (50) among study participants, Greene notes. For this reason, 80 percent is not a totally precise estimate of the reduction in risk obtained by surgery. The actual reduction in risk could be either somewhat more or somewhat less than 80 percent.
“Nonetheless, there is no doubt that [for women at high risk] salpingo-oophorectomy eliminates most of the risk of ovarian and fallopian tube cancer, and represents an invaluable option in the management of [this high-risk population],” he concludes.