Ovarian Cancer Gene May Point to Early Removal of Ovaries: Study

In particular, women with BRCA1 mutation should have surgery by age 35, researchers say

Monday, February 24, 2014

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MONDAY, Feb. 24, 2014 (HealthDay News) -- Women who carry a BRCA1 gene mutation and have their ovaries removed by age 35 appear to dramatically reduce their odds of developing ovarian cancer and dying, a new international study finds.

Having this procedure, called oophorectomy, may reduce the odds of dying by age 70 by about 77 percent, researchers say. Women who have BRCA1 or BRCA2 gene mutations are at greater risk of developing breast and/or ovarian cancer.

"We have a strong basis to recommend that women who have a BRCA1 mutation really benefit from having an oophorectomy, and they should have it by age 35," said lead researcher Dr. Steven Narod, a professor of medicine at the University of Toronto, in Canada.

Women with BRCA2 mutations can delay surgery until they're 40, since their risk of ovarian cancer is not as strong, he added.

The procedure made news last year when film star Angelina Jolie, a carrier of the BRCA1 mutation, announced plans to have her ovaries removed. Previously, she had undergone a preventive double mastectomy. Jolie's mother, actress Marcheline Bertrand, died of ovarian cancer at the age of 56.

Study author Narod noted that the benefits of the surgery outweigh the side effects. Those side effects include menopause symptoms, such as hot flashes and sleep disturbances, which can be managed by hormone replacement therapy, he said.

Other side effects may include a small increase in the risk for heart disease and possibly memory and thinking problems. Of course, removing the ovaries means not having children, but by 35 the women could have already started a family, Narod said.

The real challenge, Narod added, is getting women screened for BRCA mutations. Most women who have these mutations don't know they have them. "Probably only one in 300 women carry these mutations," he said.

"If we are going to get the full impact, it's important that more women get tested," Narod said. But making genetic testing more available means lowering the cost from around $1,000 to $100, he added.

Narod's team is currently running pilot programs in Iceland and Bermuda testing every woman who has a mammogram for BRCA mutations as well.

Ovarian cancer is often called the "silent killer" because symptoms may not appear until the cancer had spread. In 2013, the U.S. National Cancer Institute estimated that 22,240 women would be diagnosed with the disease that year and 14,030 would die from it.

This is why in the United States, as many as 70 percent of women who know they carry BRCA mutations choose to have their ovaries removed, the researchers noted.

The report was published Feb. 24 in the Journal of Clinical Oncology.

For the study, researchers from North America and Europe used an international registry to identify 5,783 women who carried mutations of the BRCA genes.

Among these women, 2,270 did not have their ovaries removed. Another 2,123 had already had the surgery at the start of the study, and 1,390 women had surgery during the study follow-up period from 1995 to 2011.

During an average follow-up of 5.6 years, 186 women developed either ovarian cancer, fallopian tube cancer or peritoneal cancer (cancer of the abdominal lining that covers the uterus), the researchers found.

Narod's group reported that women who had their ovaries removed reduced their risk of ovarian cancer by 80 percent. Among women with a BRCA1 mutation, delaying the surgery until age 40 increased the risk of ovarian cancer by 4 percent and the risk increased 14.2 percent if a woman waited until age 50 before having the operation.

For women with the BRCA2 mutation alone, however, the risk of developing ovarian cancer was very low. Among such women in the study, only one developed ovarian cancer.

The researchers noted that the lifetime risk of ovarian cancer among all women -- including those without BRCA mutations -- is only 1.4 percent.

During the study, 511 women died: 333 died of breast cancer, 68 from ovarian, fallopian tube or peritoneal cancers, and the rest from other causes.

In total, having the ovaries removed reduced the risk of death from any cause by 77 percent. The majority of this reduction comes from the reduced risk of ovarian, fallopian tube, peritoneal and breast cancers, the researchers explained.

In a previous study, Narod's group found that removing the ovaries also reduced the risk of breast cancer by 48 percent in women with a BRCA1 mutation, and the risk of dying from breast cancer by 70 percent in women diagnosed with the disease, according to an American Society of Clinical Oncology news release.

Dr. Andrew Menzin, the associate chief of gynecologic oncology at North Shore-LIJ Cancer Institute in Manhasset, N.Y., said the new study "provides strong support for this intervention and can help people decide, in the context of their lives, what to do."

Menzin, who was not involved with the study, said that women with a family history of breast or ovarian cancer should be screened by their primary care doctor.

Since genetic testing has not only medical but also other implications -- such as the anxiety it can cause -- it should only be done along with genetic counseling to interpret the results, he noted. "It's a combination of the science of medicine and the art of medicine," he said.

SOURCES: Steven Narod, M.D., professor of medicine, University of Toronto, Canada; Andrew Menzin, M.D., associate chief, gynecologic oncology, North Shore-LIJ Cancer Institute, Manhasset, N.Y.; American Society of Clinical Oncology, news release, Feb. 24, 2014; Feb. 24, 2014, Journal of Clinical Oncology

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