Prophylactic mastectomy and salpingo-oophorectomy significantly decrease mortality as well as the risks of breast and ovarian cancer among women who carry BRCA1 or BRCA2 mutations, according to a report published in the Sept. 1 issue of JAMA .
These risk-reducing surgeries benefit both carriers who have not yet developed malignancies and those who have already been treated for breast or ovarian cancer and are still at risk for further primary disease, said Dr. Susan M. Domchek of the University of Pennsylvania, Philadelphia, and her associates.
Most previous studies that examined whether the prophylactic excisions actually impact mortality did not address their efficacy according to subjects’ mutation status or prior cancer diagnosis. With no proof of such efficacy, some clinicians and patients may have avoided the surgeries. Some may have believed that the excisions conferred little added protection against further malignancies, especially in the setting of chemotherapy-induced menopause or hormonal therapy, Dr. Domchek and her colleagues said.
The investigators assessed outcomes in a cohort of 2,482 BRCA1 and BRCA2 mutation carriers identified at 22 medical centers in North America and Europe that were participating in the Prevention and Observation of Surgical Endpoints (PROSE) consortium. The study subjects were enrolled in 1974-2008 and followed through the end of 2009 (median follow-up, 3.65 years).
Approximately 10% of these women underwent prophylactic mastectomy, and 40% underwent prophylactic salpingo-oophorectomy.
No breast cancers developed in mutation carriers who underwent prophylactic mastectomy, whereas breast cancers did develop in 7% of those who declined prophylactic mastectomy. This confirms that prophylactic mastectomy is highly effective at significantly reducing breast cancer in women at high risk, the investigators said (JAMA 2010;304:967-75).
Among women who underwent prophylactic salpingo-oophorectomy, only 1% subsequently developed ovarian cancer, and only 11% subsequently developed breast cancer. In contrast, among women who declined prophylactic salpingo-oophorectomy, about 6% subsequently developed ovarian cancer, and 19% subsequently developed breast cancer.
Prophylactic salpingo-oophorectomy cut the risk of ovarian cancer by 70% in the subgroup of women who did not have prior breast cancer and decreased it even further, by 85%, in those who did have prior breast cancer. This finding illustrates why breast cancer patients may want to know about their BRCA mutation status even if they have undergone bilateral mastectomy: Prophylactic salpingo-oophorectomy may well protect them from developing a new primary malignancy in the ovaries.
Among women with no prior breast cancer, prophylactic salpingo-oophorectomy reduced breast cancer risk by 37% in carriers of the BRCA1 mutation and by 64% in carriers of the BRCA2 mutation.
Prophylactic salpingo-oophorectomy also decreased all-cause mortality, which was only 3% among women who underwent the procedure, compared with about 10% among those who did not. The prophylactic excision also significantly reduced breast cancer mortality (2% vs. 6%) and ovarian cancer mortality (0.4% vs. 3%), compared with no prophylactic salpingo-oophorectomy.
In an editorial accompanying this report, Dr. Laura Esserman and Dr. Virginia Kaklamani said that only 10% of the subjects in this study chose prophylactic mastectomy, and only 38% chose prophylactic salpingo-oophorectomy (JAMA 2010;304:1011-2). Now that the study results confirm that these procedures reduce not just cancer risk but also mortality, “women who test positive for BRCA1 or BRCA2 can make more informed choices about whether to consider prophylactic surgery or to opt for intensive surveillance,” and “women considering prophylactic interventions should be aware that options have changed and improved,” the physicians wrote.
Laparoscopic salpingo-oophorectomy in this setting is relatively low risk and can be done on an outpatient basis; invasive node sampling is no longer required as part of the procedure, said Dr. Esserman of the University of California, San Francisco, and Dr. Kaklamani of Northwestern University, Chicago.
Cosmetic options also have improved for prophylactic mastectomy. A total skin-sparing approach provides a more natural appearance, is safe and reliable, and now is routine in many major breast centers.
For women who worry that positive results on genetic testing will raise their insurance premiums, clinicians can reassure them that the Genetic Information Nondiscrimination Act of 2008 protects them from insurance and employer discrimination based on genetic profiles, said Dr. Esserman and Dr. Kaklamani.
Among the institutions providing support for the study were the University of Pennsylvania, the U.S. National Cancer Institute, the Cancer Genetics Network, the Dana-Farber/Harvard Cancer Center, and the U.K. National Institute for Health Research. Dr. Domchek, Dr. Esserman, and Dr. Kaklamani reported no financial conflicts of interest.