Radical Surgery Reduces Ovarian Cancer Risk

TORONTO, July 11 -- Women with harmful mutations in the two major susceptibility genes linked to breast cancer can sharply reduce their risk of an ovarian malignancy by having their ovaries and fallopian tubes removed, according to researchers here.

The procedure - a bilateral salpingo-oophorectomy - reduces the risk of cancer by 80% in women with mutations in the BRCA1 and BRCA2 genes, according to Steven Narod, M.D., of the Centre for Research in Women's Health here.

The residual risk is for cancer of the peritoneum, which cannot be surgically removed, Dr. Narod and colleagues reported in the July 12 issue of the Journal of the American Medical Association. Dr. Narod was one of the investigators who first identified BRCA1 as a familial breast cancer gene.

"This is good as surgery is going to get," Dr. Narod said in an interview. "Any further reduction in risk is going to be made by non-surgical means."

Cancers of the ovaries, fallopian tubes, and peritoneum are usually lumped together as ovarian cancer, he said. "It's only when we do surgery at the early stages that we can distinguish them," Dr. Narod added.

The current findings come from a continuing prospective study, begun in 1992, of women identified with BRCA1 and BRCA2 mutations and treated at one of 32 centers in Canada, the U.S., Europe, and Israel. A total of 1,828 carriers completed questionnaires at baseline and during follow-up and were observed from the date they entered the study until diagnosis of one of the three forms of cancer, death, or until they completed a follow-up questionnaire. Mean follow-up was 3.5 years.

Of the 1,828, 30% -- or 555 - had already had a bilateral salpingo-oophorectomy at the time they entered the study. Another 27% (or 490) had the procedure after they entered the study, and the remaining 43% (783) did not have surgery.

During the follow-up, there were 50 incident ovarian, fallopian tube, and peritoneal cancers in the cohort. Of those, 32 were among the women with intact ovaries, Dr. Narod and colleagues reported, 11 were found at the time of the bilateral salpingo-oophorectomy, and seven were diagnosed after the procedure.

The observed incidence of cancer among the women with intact ovaries was 1,015 per 100,000 per year - about 58 times the incidence in the general population, the researchers reported. By contrast, the incidence among women who had a prophylactic bilateral salpingo-oophorectomy was 217 per 100,000 per year (4.3%)- only 9.3 times the expected rate for the general population.

After adjusting for various factors, Dr. Narod and colleagues said, the procedure reduced the risk of cancer by 80%: the hazard ratio was 0.20, with a 95% confidence interval between 0.07 and 0.58, which was statistically significant at P=0.003.

The authors pointed out that the residual risk for peritoneal cancer of 4.3% may have been overestimated as three cases were diagnosed within three years of surgery. Thus, it is possible that these are actually metastases of subclinical disease that was present at the time of surgery.

Women with mutations in BRCA1 and BRCA2 are at sharply increased risk for ovarian cancer, and it is standard practice for physicians to recommend a salpingo-oophorectomy, but only about 60% of women follow through and have the surgery. "I would like to see it be 100%," Dr. Narod said, as soon as women are at or near the end of their child-bearing years.

"These cancers are not detectable early, the mortality rate is 80% -- if they get it most people succumb to it - and they can't be screened for," he said. "So that leaves prevention."