Preventative Ovarian Surgery in BRCA1 Mutation Carriers More Beneficial Before Age 35

Steven Narod, MD

For the first time, physicians have a clearer understanding of the optimum age for prophylactic oophorectomy in patients with BRCA mutations who want to reduce their risk of ovarian, fallopian tube, and breast cancer, according to a study published in the Journal of Clinical Oncology.

The study showed that waiting to undergo prophylactic oophorectomy until after the age of 35 significantly increased the risk of developing ovarian cancer for women with BRCA1 mutations. Moreover, women with BRCA1 or BRCA2 mutations with no cancer at baseline who underwent oophorectomy experienced a 77% reduction in their overall risk of death by age 70. The study also demonstrated that women who harbor only the BRCA2 mutation do not appear to be at an increased risk by age 35 and can delay surgery until their 40s.

"To me, waiting to have oophorectomy until after 35 is too much of a chance to take," Steven Narod, MD, professor of medicine at the University of Toronto in Canada and the study's lead author, said in a press release. "These data are so striking that we believe prophylactic oophorectomy by age 35 should become a universal standard for women with BRCA1 mutations."

In the study, 5783 women with either BRCA1 (n=4473) or BRCA2 (n=1310) mutations were selected from centers in Canada, the United States, Austria, France, Italy, Norway, and Poland. The women were asked to complete questionnaires about their reproductive history, surgical history (including preventive oophorectomy and mastectomy), and hormone use.

Among the 5783 women, 2270 did not have an oophorectomy, 2123 had an oophorectomy before the study began, and 1390 underwent oophorectomy during the study follow-up period.

After an average follow-up period of 5.6 years (with some women followed as long as 16 years), 186 women developed either ovarian (n =132), fallopian (n =22), or peritoneal (n =32) cancer, of which 68 have died.

The results of the study showed that oophorectomy reduced the risk of ovarian, fallopian tube, or peritoneal cancer in BRCA1 or BRCA2 carriers by 80% (hazard ration [HR]=0.20; 95% CI, 0.13 - 0.30; P <.001)]. There was also a 77% reduction in all-cause mortality at age 70 [HR=0.23; 95% CI, 0.13 - 0.39; P < .001)] in the patients who underwent oophorectomy.

The authors of the study found that if a woman with a BRCA1 mutation delays prophylactic surgery until age 40, her risk of ovarian cancer is raised to 4%. The risk developing ovarian cancer jumps to 14.2% if a woman with a BRCA1 mutation waits until age 50.

For patients with BRCA2 mutations, there was only one case of ovarian cancer diagnosed before age 50, the authors of the study said.

The lifetime risk of ovarian cancer in all women (including those without BRCA mutations) is 1.4%. About 10% to 15% of ovarian cancers occur because of a genetic mutation, according to cancer.net.

“These results could make a real difference for women with BRCA mutations, who face tough decisions about whether and when to undergo a prophylactic oophorectomy. For women with BRCA1 mutations, these results suggest that surgery should be performed as soon as it is practical,” Don Dizon, MD, assistant in medicine, Medical Gynecologic Oncology, Massachusetts General Hospital said in a press release. “Importantly, for women who will be undergoing this surgery early in life, it's reassuring to see that it carries long-lasting benefits, substantially reducing ovarian cancer risk as well as total mortality risk.”