Preventive Ovarian Surgery in BRCA1 Mutation Carriers Should Be Performed Early for Greatest Cancer Risk Reduction

JCO Research Round Up
February 24, 2014

Surgery Also Lowers Risk of Death Due to Any Cause for All BRCA Mutation Carriers

A large, long-term study showed for the first time that women with BRCA1 mutations should undergo preventive surgical removal of the ovaries (prophylactic oophorectomy) by age 35 to achieve the greatest reduction in ovarian cancer risk. Researchers showed that waiting until a later age to have the surgery was associated with a significantly higher ovarian cancer risk. In addition, the investigators reported for the first time that prophylactic oophorectomy reduces the overall risk of death by 77 percent among women with either a BRCA1 or BRCA2 mutation.

In the Hereditary Ovarian Cancer Clinical Study, researchers from several countries identified 5,787 women with BRCA mutations from an international registry; the study began in 1995, and the women were followed through 2011.

Overall, the researchers found that prophylactic oophorectomy reduced the risk of ovarian cancer by 80 percent.  Among women who were BRCA1 mutation carriers, the risk of developing ovarian cancer increased for those who underwent surgery at a later age: the risk of ovarian cancer was 4 percent for those who had surgery at age 40; ovarian cancer risk increased to 14.2 percent for women who waited until age 50 to have the surgery. By comparison, the lifetime risk of ovarian cancer in all women (including those without BRCA mutations) is only 1.4 percent. Only one case of ovarian cancer was diagnosed before age 50 among BRCA2 mutation carriers in this study, suggesting that women with BRCA2 mutations may safely delay surgery until their 40s.

According to the researchers, the 77 percent reduction in the overall risk of death achieved with ovarian surgery was due largely to lower rates of death from ovarian, fallopian tube, peritoneal, and breast cancers. They emphasized that the benefit of this surgery may be even greater than the benefit of chemotherapy for a cancer, and that this benefit was equally strong for both BRCA1 and BRCA2 mutation carriers.

What This Means for Patients

The vast majority of women in the United States have normal forms of the BRCA genes.  These genes are known to be "tumor suppressor genes," which inhibit cancer growth, especially for breast and ovarian cancers. But a mutated BRCA gene loses this function.

As many as 70 percent of women in the United States who learn they have a BRCA mutation choose to have prophylactic oophorectomy to reduce their cancer risk. Historically, doctors have recommended that such women undergo surgery by age 35 or when they have finished having children. However, until this study, neither the optimum age for having this preventive surgery nor the benefit of the surgery on the overall risk of death had been adequately explored.

The researchers believe this study reinforces the benefits of preventive ovarian surgery among women with BRCA mutations. It may also establish a new standard for surgery timing in women with BRCA1 mutations, showing that delaying surgery beyond age 35 carries an increased risk. Women with BRCA2 mutations, however, may safely delay surgery until their 40s, since their ovarian cancer risk is not as elevated.

Women with BRCA mutations should speak with their doctors as well as a genetic counselor about their individual cancer risk and the benefits of preventive ovarian surgery and optimal timing.

Helpful Links from Cancer.Net:

Hereditary Breast and Ovarian Cancer

Ovarian Cancer: Risk Factors and Prevention

Understanding Cancer Risk

The Genetics of Cancer