A summary of a large study concluded that women with BRCA1 genetic mutations should undergo preventive ovarian surgery by age 35 to achieve the greatest reduction in their risks of breast and ovarian cancer.
The study also found that women with mutations in the BRCA1 or BRCA2 genes who had this surgery experienced a 77 percent reduction in their overall risk of death by age 70.
The large, international prospective study, published in the Journal of Clinical Oncology, suggests that waiting until a later age appears to increase the risk of ovarian cancer before or at the time of the preventive surgery. Women with a BRCA2 mutation, however, do not appear to be at an increased risk by age 35, suggesting they may delay this procedure until later.
Prior studies have shown that prophylactic oophorectomy reduces the risk of developing breast and ovarian cancers in women with BRCA1 or BRCA2 mutations. This study is the first to show an overall mortality reduction benefit. As many as 70 percent of women in the U.S. who learn they have BRCA mutations choose to have prophylactic oophorectomy.
In the Hereditary Ovarian Cancer Clinical Study, researchers from Canada, the U.S., Poland, Norway, Austria, France, and Italy identified women with BRCA mutations from an international registry, 5,787 of whom completed questionnaires about their reproductive history, surgical history (including preventive oophorectomy and mastectomy), and hormone use.
The study began in 1995, and the women were followed through 2011. Investigators examined the relationship between prophylactic oophorectomy and the rates of ovarian, fallopian tube, and primary peritoneal cancer, and the overall rate of death by age 70.
Among the 5,787 women, 2,274 did not have oophorectomy, 2,123 had already had the surgery when they began the study, and 1,390 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, fallopian tube, or peritoneal cancer.
Overall, the investigators found that oophorectomy reduced the risk of ovarian cancer by 80 percent. For women who carry a BRCA1 mutation, the authors estimate that delaying the surgery until age 40 raised the risk of ovarian cancer to 4 percent; ovarian cancer risk increased to 14.2 percent if a woman waited until age 50 to have the surgery.
In contrast, only one case of ovarian cancer was diagnosed before age 50 among BRCA2 mutation carriers in this study. By comparison, the lifetime risk of ovarian cancer in all women (including those without BRCA mutations) is only 1.4 percent.
Of the 511 women who died during this study, 333 died of breast cancer, 68 from ovarian, fallopian tube, or peritoneal cancers, and the remainder from other causes. Prophylactic oophorectomy reduced the risk of death by any cause by 77 percent, largely by lowering the risks of ovarian, fallopian tube, peritoneal, and breast cancers.
