Risk-Reducing Mastectomy Questioned for BRCA Mutation Carriers With Prior Ovarian Cancer

Mutations in the BRCA gene correspond to a higher lifetime risk of developing breast and ovarian cancers, and many women who carry these mutations consider undergoing mastectomy or salpingo-oophorectomy as preventive measures.

But for the subset of women with BRCA mutations who have already had ovarian cancer, risk-reducing mastectomy might not be worth the cost. New research from the Duke Cancer Institute found that, for many women in this unique group, prophylactic mastectomy does not produce a substantial survival gain and is not cost effective.

The finding is especially noteworthy because of updated National Comprehensive Cancer Network guidelines recommending that many women with ovarian cancer be considered for genetic testing regardless of family history. Now, more than ever before, some women with ovarian cancer are also learning that they carry a BRCA mutation.

“Risk-reducing mastectomy is costly and can require many months of follow-up and recovery,” says Charlotte Gamble, MD, the study’s lead author and a resident physician at Duke. “Our results emphasize that prophylactic mastectomy should be used selectively in women with both a BRCA mutation and a history of ovarian cancer.”

In the study, published online on July 11, 2017, in the Annals of Surgical Oncology, Gamble and co-researchers constructed a statistical model comparing risk-reducing mastectomy to breast cancer screening that included mammogram and MRI. The model incorporated clinical factors such as the age at ovarian cancer diagnosis, time between ovarian cancer diagnosis and risk-reducing mastectomy, BRCA mutation status, cancer survival rates, and treatment costs. Risk-reducing mastectomy was compared to breast cancer screening performed every 6 months following ovarian cancer diagnosis.

The study’s authors also considered the incremental cost-effectiveness ratio, using $100,000 per year of life saved as the threshold for cost effectiveness.

According to the analysis, the benefit of risk-reducing mastectomy versus screening alone largely depended on the patient’s age at the time of ovarian cancer diagnosis and time to mastectomy:

• For women diagnosed at any age with BRCA 1 and 2 gene mutations and within the first 4 years after ovarian cancer diagnosis, prophylactic mastectomy was associated with a negligible gain in survival and was therefore not found to be cost effective
• For women diagnosed at age 60 or older, regardless of time since ovarian cancer diagnosis, the gain in survival months was also negligible, and the procedure was not cost effective
• For women diagnosed at age 40 to 50 with BRCA 1 and 2 mutations at least 5 years after an ovarian cancer diagnosis, the procedure was associated with a 2- to 5-month survival benefit over screening and was found to be cost effective

“Our study provides clarity on how a woman’s age and the timing of a risk-reducing mastectomy after an ovarian cancer diagnosis impact the benefit of this procedure,” Gamble says. “Within the first 5 years, nobody benefitted from risk-reducing mastectomy, and after that threshold, survival gains were seen mostly in the youngest, healthiest ovarian cancer patients.”

“There is no right or wrong answer on how to manage breast cancer risk in this unique population,” adds senior author Rachel Greenup, MD, a surgical oncologist at Duke. “However, we hope that our findings provide guidance to women and their doctors deciding if and when prophylactic mastectomy is beneficial following ovarian cancer treatment.”