The study is the largest to date to find advantages for preventive surgery for women who carry BRCA gene mutations. Women with the faulty genes have a dramatically higher cancer risk than other women - five times greater for breast cancer and at least 10 times greater for ovarian cancer.
The study, appearing in Wednesday's Journal of the American Medical Association, found benefits for women with two different BRCA gene variants whether they had previously had breast cancer or not.
The results offer more tailored evidence for women considering ovary removal, a surgery that ends fertility, fast-forwards them into early menopause and may contribute to osteoporosis or heart problems later in life.
"It's really critical to have the best information when making such a profound decision," said senior author Timothy Rebbeck of the University of Pennsylvania School of Medicine.
The researchers followed nearly 2,500 women with BRCA mutations in Austria, England, the Netherlands and the United States. All the women were cancer-free at the start. They were watched for an average of four years. Most of the women were younger than 50 at the start of the study.
They got counseling to help them choose between surgery or increased screening to watch for cancers early.
Ten percent of the women chose mastectomy and 40 percent chose to have their ovaries removed; some had both. More than half the women had neither surgery.
The women who chose ovary removal had impressive results:
-1 percent were later diagnosed with ovarian cancer that showed up in cells missed by surgeons, compared to 6 percent of the women who kept their ovaries.
-11 percent were diagnosed with breast cancer, compared to 19 percent of the women who kept their ovaries.
-3 percent of those who had surgery died, compared to 10 percent of the others.
The study also found preventive mastectomy lowered the risk of breast cancer. No breast cancers were seen in the women who had their breasts removed. That may seem unsurprising, but mastectomy can leave behind breast tissue that can turn cancerous.
The study was observational, meaning it can't prove one choice was better than another. Other factors could have caused differences in the women's cancer rates.
But the results will help doctors counsel their patients, said Dr. Virginia Kaklamani of Northwestern University's Feinberg School of Medicine in Chicago, who wrote an accompanying editorial in the journal.
"I'll use it mostly in talking to people considering genetic testing," Kaklamani said. "I can tell them, 'If we know you test positive, there are things to do that will help you live longer."'
The increased risk for BRCA carriers is frightening. In the general population, about 12 in 100 women will get breast cancer during their lifetimes, compared to about 60 in 100 women who have faulty BRCA genes, according to the National Cancer Institute. For ovarian cancer, the lifetime risk in the general population is a little more than 1 in 100 compared to 15-to-40 in 100 women with BRCA mutations.
For women with a family history of breast or ovarian cancer, the decision to get tested can be agonizing. The $3,300 blood test, while often covered by insurance, can disrupt families, force decisions on childbearing and leave a woman feeling stigmatized. Surgery costs thousands of dollars, not including lost time at work. Without preventive surgery, a woman faces a regimen of mammograms, MRIs and blood tests to look for cancer.
But several signs point to "the beginning of a new era" for high-risk women, said Joanna Rudnick, a 36-year-old Los Angeles filmmaker. She has known for nine years that she carries a breast cancer gene mutation. Engaged and planning to have children, she's also planning to have her breasts and ovaries removed when she's 40. Her documentary "In the Family" tells about her choices and those faced by other "BRCA-positive" women.
With testing more than a decade old, researchers are just beginning to have better data to understand the benefits of risk-reducing surgery. For high-risk women, equally important are the breakthroughs in cosmetic breast reconstruction, laws to prevent genetic discrimination and evolving attitudes toward removing body parts to avoid cancer, Rudnick said. A federal judge recently struck down patents on the two genes held by Myriad Genetics Inc., which may widen research possibilities and testing options.
Rudnick's glad to hear ovary removal may reduce her risk of breast cancer as well as ovarian cancer.
"This is one of the rare silver linings that has been learned from these prospective studies," Rudnick said.