Removing ovaries cuts risk of death but causes serious side effects.
 

Angelina Jolie announced that she underwent a preventive mastectomy after learning she carried high-risk genes for breast cancer. She has not said whether she has removed her ovaries, as well, a surgery that reduces both breast and ovarian cancer risk.
 

Women who inherit mutations in high-risk genes that sharply increase the risk of breast or ovarian cancer can reduce their risk of death by 77% by having their ovaries removed by age 35, a new study shows.

The study involved mutations in the genes BRCA1 and BRCA2, which cause 5% to 10% of breast cancers and 15% of ovarian cancers, according to the National Cancer Institute.

Up to 70% of women who learn that they carry these mutations choose to have their ovaries removed to reduce the risk of ovarian and breast cancer, research shows.

In the study, in Monday's Journal of Clinical Oncology, surgery offered different benefits based on the exact mutation.

Women with a mutation in the gene BRCA1 get the clearest benefit to ovary-removal surgery by age 35, says study author Steven Narod, a professor of medicine at the University of Toronto. His study didn't find any ovarian cancers in women with BRCA2 mutations until age 40. So BRCA2 carriers can likely wait until age 40 for ovarian removal, he says.

In some cases, women who had their ovaries removed later learned that they already had ovarian cancer. But because these cancers were generally found early – before they caused symptoms – survival was very high, with 92% of women living at least five years after diagnosis, the study shows.

Among women who didn't have their ovaries removed, and who were diagnosed with ovarian cancer after symptoms appeared, only 35% were alive 10 years later, Narod says.

Narod says his study sends a very clear message: "If you want to get your risk as close to zero as you can get it, you'd better have the surgery."

For mutation carriers, removing the ovaries also cuts the risk of breast cancer in half, because the ovaries make hormones that drive breast tumor growth.

Many women with BRCA mutations, such as actress Angelina Jolie, also undergo preventive mastectomies to reduce their risk of breast cancer.

But removing the ovaries at such a young age carries heavy costs in terms of quality of life, says Noah Kauff, director of ovarian cancer screening and prevention at Memorial Sloan Kettering Cancer Center in New York, who wasn't involved in the study. It puts an end to childbearing and plunges women instantly into menopause, which can cause disruptive symptoms such as hot flashes, while also increasing the long-term risks of heart disease and bone fractures.

Researchers considered these increased risks but still found a huge drop in mortality before age 70, Narod says. Researchers didn't estimate the risk of death after age 70, because by that age, women are at increased risk of death from many causes, Narod says.

Kauff says the study may overestimate the benefits from ovarian removal, however. That's because 60% of the women who had ovary surgery had the organs removed before the study began. Women with very aggressive ovarian cancers, detected only during surgery, would never have made it into the study, he says.

Kauff also says he's concerned the study will scare young women into having surgery before they're ready. Although BRCA1 mutation carriers who had their ovaries removed between age 40 and 49 had a 3.8% risk of cancer, Kauff notes that their cancers were often curable.

The study notes that even surgeries to remove the ovaries and fallopian tubes, which connect the ovaries to the uterus, don't completely reduce the risk. That's because ovarian cancer also can occur in the peritoneum, or lining of the abdomen. About 4% of women with BRCA1 mutations developed peritoneal cancer within 20 years of removing their ovaries, the study says. Likewise, women who have double mastectomies have a small risk of developing breast cancer, especially in the small amount of breast tissue under the armpit.

Narod notes that women who aren't ready for surgery have other options. Women can take the drug tamoxifen to reduce their risk of breast cancer, he says. And ordinary birth control pills cut the risk of ovarian cancer in half, whether or not women have BRCA mutations, Narod says. Kauff notes that mutation carriers who don't want to have a mastectomy can opt for frequent screenings with mammograms and MRIs.

Sue Friedman discovered she carried a BRCA2 mutation after being diagnosed with breast cancer at age 33. She had her ovaries out at age 35, a decision that prevented her from having the second child she had hoped for.

"Nobody then was talking about fertility options," says Friedman, of Tampa, Fla., founder of FORCE, an advocacy group for BRCA mutation carriers. "I did not want to hear 'You have cancer' ever again."

Today, Friedman, 50, takes hormone therapy to manage her symptoms – an unpopular decision with many doctors, who say the pills increase her risk of recurrence – but is healthy enough to have recently run her first marathon. Kauff says studies suggest it is much safer to take hormone therapy if mutation carriers have not had cancer.

"These are tough decisions," says Friedman, whose group helped doctors recruit patients for the study. "Survival is not the only outcome. Quality of life matters, too."