Prophylactic Surgery Recommended for BRCA1 Carriers

Prophylactic surgery to remove the ovaries, called oophorectomy, significantly lowers the risk of ovarian and breast cancers, lowers mortality from previous breast cancer, and lowers all-cause mortality in women with BRCA1 and BRCA2 mutations, a recent study concludes.

“The data is strong enough that we can recommend salpingo-oophorectomy by age 35 for BRCA1 carriers across the board,” says Steven Narod, MD, PhD, professor in the Dalla Lana School of Public Health and Department of Medicine at the University of Toronto in Canada and the study's lead investigator. “For women who have had breast cancer in the past, oophorectomy lowers their risk of dying from breast cancer. It has a preventative role and a therapeutic one.” Salpingo-oophorectomy involves removing both the fallopian tubes and ovaries and is the current standard of care.

In the study, published in the Journal of Clinical Oncology, researchers from North America and Europe used an international registry to identify 5,783 women with BRCA1 or BRCA2 mutations. After an average follow-up of 5.6 years, they found that preventative surgery was associated with an 80% reduction in the risk of ovarian, fallopian tube, and peritoneal cancers, and a 77% decrease in all-cause mortality up to age 70.

Notably, the study found that waiting until age 40 (versus age 35) to undergo oophorectomy increased BRCA1 carriers' risk of developing ovarian cancer from 1.5% to 4%, while waiting until age 50 increased the risk to 14.2%. By comparison, the lifetime risk of ovarian cancer in all women, including those without BRCA mutations, is 1.4%.

Although the impact of oophorectomy on mortality in the study was mainly due to the reduced incidence of ovarian, tubal, and peritoneal cancers, the surgery also lowered the risk of death in women with a history of breast cancer, says Narod. The results build on findings from a previous study by Narod's team, which found that oophorectomy reduces the risk of breast cancer by 48% in women with BRCA1 mutations and, once breast cancer is diagnosed, lowers the risk of mortality by 70%.

The researchers also analyzed the impact of oophorectomy on all-cause mortality up to age 70 in women who had been treated for breast cancer. They found that oophorectomy reduced the risk of death by 74% in women who had the surgery before or within 3 years of diagnosis, and by 61% for those who had it more than 3 years after diagnosis.

Findings from a separate study published last month in Proceedings of the National Academy of Sciences bolster the case for oophorectomy as an effective therapeutic option for women with a family history of breast cancer, says Narod. In that study, researchers concluded that estrogen promotes survival of BRCA1-deficient cells, which explains why oophorectomy, which dramatically decreases estrogen levels, significantly reduces breast cancer risk and recurrence in women with BRCA1 mutations.

“Two really important questions are what makes oophorectomy so effective for BRCA cancers and whether other women may also benefit,” says Narod. “At this point, BRCA carriers are the only women who should have prophylactic oophorectomy, but there may be other groups who could benefit from this surgery.”

Eventually, researchers hope to be able to identify which women would benefit from oophorectomy based on genetic characteristics of individual tumors. “We might one day be able to test the tissue of anyone with premenopausal breast cancer to predict her response to oophorectomy,” he says.