Surgical option: removal of ovaries can prevent cancers in women at risk. (This Week).

Harboring a mutation in either the BRCA1 or BRCA2 gene is known to place a woman at high risk of developing breast and ovarian cancers. Less clear is what a woman with such a mutation should do about it.

Some physicians have offered a drastic measure--ovary removal--as a preventive strategy. Although few studies have explored its value, ovary removal appeals to some doctors and their patients since it eliminates tissue that's targeted by ovarian cancer. It also removes tissue that produces estrogen, the hormone that promotes breast and ovarian cancers.

Two studies now provide the best evidence to date that ovary removal, or oophorectomy, in women carrying a BRCA mutation significantly reduces the incidence of cancer of the ovaries and peritoneum, the membrane that lines the abdomen. The data also suggest that the surgery prevents breast cancer in some women.

In a study conducted at Memorial Sloane Kettering Cancer Center in New York, researchers tracked the progress of 170 women carrying one of the mutations. Of these, 98 elected to undergo oophorectomy and 72 didn't. Over 2 years of follow-up, five of the nonsurgery group, but only one of those getting surgery, were diagnosed with cancer of the ovaries or peritoneum, Kenneth Offit and his colleagues report in the May 23 New England Journal of Medicine (NFJM).

Peritoneal cells closely resemble cells that coat the ovaries, and some peritoneal cancers appear to arise from ovarian tissue left over after oophorectomy, says physician Daniel Haber of Massachusetts General Hospital in Charlestown in the same issue of NEJM.

This study offers the first clear evidence that ovary removal in women with BRCA mutations protects against peritoneal cancer, says Lynn C. Hartmann, a medical oncologist at the Mayo Clinic in Rochester, Minn.

Offit, a cancer geneticist, and his colleagues also note that 17 percent of the women foregoing surgery developed breast or gynecologic cancers, whereas only 4 percent of those in the surgery group had such malignancies.

In the other study, epidemiologist Timothy R. Rebbeck of the University of Pennsylvania School of Medicine in Philadelphia and his colleagues reviewed 8-year medical histories of 551 women with a BRCA mutation. Of 292 women who hadn't had an oophorectomy, 58 women--20 percent--had developed ovarian cancer or peritoneal cancer over that time. Of 259 who had the operation at the beginning of the period, none developed ovarian cancer and only two women developed peritoneal cancer. Breast cancer incidence was halved for women who had their ovaries removed, compared with those who opted out of surgery.

Ovarian cancer is deadly because it can go unnoticed for years while it spreads. The rate of ovarian cancer in U.S. women is at least 1 in 75 over a lifetime, but the risk jumps to as high as 2 in 5 women with a BRCA mutation.

The findings in the two studies suggest that oophorectomy performed soon after a woman's childbearing years end could eliminate nascent ovarian cancer if she harbors a BRCA mutation, Rebbeck says. Indeed, of the 259 women who chose surgery, 6 were discovered at the time of the operation to have ovarian cancer. All of these cases were previously undetected and in an early stage, Rebbeck says.

The research "supports the idea that removing the ovaries makes a big difference" in women carrying a BRCA mutation, says Wylie Burke, a physician and geneticist at the University of Washington School of Medicine in Seattle.

The work, says Burke, also suggests that ovary removal might be a wise course for some women who don't have a BRCA mutation but who have a family history of ovarian cancer, particularly those who have a mother and a sister with the disease.

Oophorectomy is major surgery and therefore comes with the risk of complications. Ovary removal also stops production of estrogen, a hormone that protects women against heart disease and bone thinning. The hormonal change abruptly sends a woman into menopause. For that reason, premenopausal women undergoing the operation are usually put on hormone-replacement therapy to ease menopausal symptoms, such as hot flashes, says Offit.

While it seems counterintuitive to give a woman who is genetically susceptible to cancer a hormone that contributes to it, he notes that the amount of estrogen given therapeutically is much less than a woman's ovaries produce before menopause.