NEW YORK (Reuters Health) - Two new studies provide strong evidence that women who have a gene mutation linked to a high risk of breast and ovarian cancer can reduce the likelihood of developing the diseases by having surgery to remove both ovaries.

"Our data are very encouraging," Dr. Timothy R. Rebbeck, of the University of Pennsylvania in Philadelphia, told Reuters Health in an interview. Rebbeck is the lead author of one of two reports in the May 23rd issue of The New England Journal of Medicine.

He noted that women with a BRCA1 or BRCA2 mutation, both of which are known to increase the risk of breast and ovarian cancers, are often advised to consider having their ovaries removed after they complete childbearing.

The two studies "provide some concrete data to support that decision," he said.

But Rebbeck stressed that most women are not good candidates for the surgery.

"This isn't something that anyone should take lightly," he said. Despite the reduced risk of breast and ovarian cancer after ovary removal, Rebbeck said that the surgery, known as oophorectomy, is "not a totally benign thing." He explained that when a woman's ovaries are removed, her body enters menopause years or even decades before she would naturally do so.

"We dont know what the long-term risks" are of having ovaries removed, Rebbeck said.

Hormone replacement therapy (HRT) can ease hot flashes and other symptoms of menopause, but the question of whether women who have an oophorectomy should take HRT until they reach the age of natural menopause remains unanswered, the Philadelphia researcher said.

Since removing the ovaries drastically lowers the levels of hormones a woman's body produces, there is some concern that HRT might raise the risk of cancer by restoring some of these hormones. However, Rebbeck pointed out that hormone levels in HRT are dwarfed by the "massive" amounts of hormones produced by the ovaries.

The hope, according to Rebbeck, is that "you're not going to wash out the protective effect" of oophorectomy with the small level of hormones in HRT. This hypothesis has not been proved yet, however, Rebbeck said.

Due to the risks involved with oophorectomy, a woman's risk of cancer "has to be balanced" against the uncertain risks of beginning menopause early in life, Rebbeck said. If a woman's genetic risk of breast and ovarian cancer is high enough, she "might be willing to take the risk," he said. But for women who do not have a high genetic risk of cancer, then surgery to remove the ovaries is not worth the risk, according to Rebbeck.

Women who carry the BRCA1 or BRCA2 mutations have a 60% to 85% risk of developing invasive breast cancer by age 70 and a 15% to 65% risk of developing invasive ovarian cancer.

Rebbeck and his colleagues found that women with one of these mutations who underwent double oophorectomy reduced their risk of ovarian cancer by 96% and their risk of breast cancer by 53%.

Based on at least 8 years of follow-up, just 8 out of the 259 women who had their ovaries removed developed ovarian cancer or a related cancer called papillary serous peritoneal carcinoma. But six of these cancer cases were detected during the ovary-removal surgery, so the actual percentage of women who developed ovarian-related cancer after surgery was less than 1%. In contrast, about 20% of women who had not had an oophorectomy developed ovarian cancer.

Rebbeck's team studied 99 of the women to see whether ovary removal also reduced the risk of breast cancer. About 21% of women who had the surgery developed breast cancer compared with about 42% of women who had not had their ovaries removed.

In the other study, a team led by Dr. Kenneth Offit at Memorial Sloan-Kettering Cancer Center in New York, found that surgery to remove both ovaries and the fallopian tubes, an operation called salpingo-oophorectomy, greatly reduced the risk of both ovarian and breast cancer. The study included 170 women aged 35 and older who had a BRCA1 or BRCA2 mutation. The women were given a choice to have their ovaries and fallopian tubes removed or to be closely monitored for signs of ovarian cancer.

During an average of about 2 years, 3 of the 98 women who had surgery were diagnosed with breast cancer and one woman developed peritoneal cancer. Among the 72 women who did not choose surgery, there were 8 new cases of breast cancer, 4 of ovarian cancer and 1 of peritoneal cancer.

The results are promising, Offit told Reuters Health in an interview, because they show that preventive removal of the ovaries can reduce the risk of both breast cancer and ovarian cancer in women at highest risk. He noted that when the BRCA mutations were identified in the mid 1990s, there was no proof that either cancer screening or preventive surgery would reduce cancer risk.

The two studies "contribute to mounting evidence" that women who carry BRCA mutations can reduce their risk of both ovarian and breast cancer by having both ovaries removed, according to Dr. Daniel Haber at Massachusetts General Hospital in Charlestown.

"Whether the resulting reduction in the risk of breast cancer, combined with intensive surveillance, is preferable to the more complete protection offered by prophylactic mastectomy is likely to remain a highly personal choice," Haber notes in a related editorial.

SOURCE: The New England Journal of Medicine 2002;346:1609-1622, 1660-

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