By Sharon Begley
NEW YORK, Feb 24 (Reuters) - Women with genetic mutations that increase their risk of ovarian cancer have fewer years than physicians thought to make the difficult choice of having their ovaries removed to prevent the often-fatal disease, according to a study published on Monday.
Current guidelines give such women by age 40 to decide, but the study's Canadian authors now recommend that decision be made by 35. earlier.
Women with BRCA1 mutations who wait until after age 35 to have a "prophylactic oophorectomy" face a five-times higher likelihood of developing ovarian cancer than those who have the surgery by that age, according to the study of 5,783 women, which was published in the Journal of Clinical Oncology. They also face a four-times higher risk of premature death compared to women who have the surgery by age 35.
Overall, oophorectomy reduced the risk of ovarian cancer by 80 percent and the risk of premature death from any cause by 77 percent.
"For women with BRCA1 mutations, these results suggest that surgery should be performed as soon as it is practical," said Dr Don Dizon, a spokesman for the American Society of Clinical Oncology. The surgery "carries long-lasting benefits, substantially reducing ovarian cancer risk as well as total mortality risk."
BRCA1 and BRCA2 are widely known as breast cancer genes, and women with a mutation in one or both often decide to have their breasts removed so they do not develop that disease. Last year actress Angelina Jolie went public with her decision to undergo prophylactic mastectomy after she tested positive for a BRCA mutation.
Mutations in the same genes also increase the risk of ovarian cancer. Removing the ovaries is not only major surgery, like mastectomy, but also triggers menopause. And it makes conceiving children impossible.
"Our strongest instincts are for survival and reproduction, and women facing this decision have to balance those," said Dr Noah Kauff, director of ovarian cancer screening and prevention at Memorial Sloan Kettering Cancer Center in New York City who was not involved in the new study.
In a 2008 study he and colleagues found that 64 percent of women with the mutations opt to have their ovaries removed. By comparison, 25 percent to 40 percent have a prophylactic mastectomy.
The findings about the benefit of ovary removal by age 35 apply to women with mutations in the BRCA1 gene, not BRCA2, suggesting that the latter women may delay such surgery.
Current guidelines give women a few more years to make the difficult decision. The American College of Obstetricians and Gynecologists recommends that the 1 in 300 to 800 women with a BRCA1 or BRCA2 mutation be offered prophylactic ovary removal by age 40 or when childbearing is complete. The National Comprehensive Cancer Network recommends an age of 35 to 40.
Studies that support those recommendations found that prophylactic oophorectomy reduces the risk of developing breast and ovarian cancers in women with BRCA1 or BRCA2 mutations. But the new research is the first to show a reduction in overall mortality.
"To me, waiting to have oophorectomy until after 35 is too much of a chance to take," said Dr Steven Narod of the University of Toronto, who led the study. "These data are so striking that we believe prophylactic oophorectomy by age 35 should become a universal standard for women with BRCA1 mutations."
Other experts are not so sure.
For one thing, the risk of ovarian cancer in BRCA1 women who waited until 40 to have their ovaries removed was still small: 1.5 percent. It was 3.8 percent for women who had the operation in their 40s and 14.2 percent in women who waited until 50. For women without a BRCA mutation, the lifetime risk of ovarian cancer is 1.4 percent.
"We've always known that the earlier oophorectomy is performed, the greater the protection against both breast and ovarian cancer," said Kauff. "But you don't fall off a cliff at age 35 or even 40."
The study, he warned, may overestimate the benefits of early oophorectomy.
Women who had an oophorectomy before age 35 but nevertheless developed an aggressive cancer and died soon thereafter were unlikely to be among the 5,783 in the study, he pointed out since they were already dead. The study was therefore blind to these women's bad outcome despite early oophorectomy and as a result overestimated the benefit of pre-35 surgery.
But even with that caveat, Kauff said, "The risk of ovarian cancer probably rises 1 to 2 percent for every year you wait beyond 40" to have an oophorectomy. (Reporting by Sharon Begley; Editing by Julie Steenhuysen and Cynthia Osterman)