New Study Links BRCA1 Mutations with Aggressive Uterine Cancer

Hysterectomy may be warranted for women with BRCA1 mutations

Mutations in the BRCA1 and BRCA2 genes have been linked to breast, ovarian, and fallopian tube cancers. According to a new report published in JAMA Oncology, women with BRCA1 mutations also have a higher risk of developing an aggressive type of uterine cancer.

“Our study provides the strongest evidence to date that BRCA1 mutations are associated with a particularly aggressive form of uterine cancer,” says Catherine A. Shu, MD, a medical oncologist at Columbia University Medical Center/NewYork-Presbyterian and first author of the report. “While the overall risk is relatively low, women with these mutations may want to talk to their surgeons about whether they should have a hysterectomy, along with other surgery, to further reduce their cancer risk.”

Until now, the role of BRCA mutations in uterine cancer had been an open question.

Dr. Shu and colleagues from nine academic medical centers in the United States and the United Kingdom enrolled more than 1,000 women with BRCA1 or BRCA2 mutations who had their ovaries and fallopian tubes removed—a surgical procedure known as risk-reducing salpingo-oopherectomy (RRSO)—but still had a uterus. Studies have shown that RRSO can substantially reduce the risk of developing breast, ovarian, and fallopian tube cancers.

The researchers followed the women (median age of 45.6 years) for several years after RRSO, comparing the incidence of uterine cancer in this group with expected uterine cancer rates, adjusted for age and race, from the Surveillance, Epidemiology, and End Results database.

The results were striking. Four of the 627 BRCA1-positive women—22 times the expected rate—developed serous uterine cancer, an aggressive type. The researchers performed a tissue analysis of three of the serous tumors and determined that a BRCA1 mutation played a direct role in the development of each of the three tumors.

Of the 453 women with BRCA2 mutations, one developed serous uterine cancer—not a statistically significant increase in risk.

Given the low complication and mortality rates associated with ovary and fallopian tube removal, the combined RRSO-hysterectomy may become the preferred risk-reducing surgical approach for women with BRCA1 mutations. However, hysterectomy may not be appropriate for women who have extensive uterine adhesions, had previous reproductive tract surgery, or may be considering a future pregnancy using assisted-reproductive approaches.

Dr. Shu is assistant professor of medicine (in oncology & hematology) at Columbia University College of Physicians & Surgeons. Her involvement in the study occurred while she was a fellow at Memorial Sloan Kettering Cancer Center.


Full results of the study were published June 30, 2016, in JAMA Oncology. Read the journal’s press release here.

The study was funded by grants from the Department of Defense Ovarian Cancer Research Program (DAMD17-03-1-0375); the National Institutes of Health (R01-CA083855 and R01-CA102776); NIH/NCI Cancer Center Support Grants (P30 CA008748, P30 CA016520, P30 CA51008, P30 CA 16042); the Prevention, Control, and Population Research Program of Memorial Sloan Kettering Cancer Center; Project Hope for Ovarian Cancer Research and Education; Eisenberg-Feinstein Fund for Gynecological Cancer Research and Treatment; Chia Family Foundation; Andrew Sabin Family Foundation; Filomena M. D’Agostino Foundation; National Institute for Health Research to the Biomedical Research Centre at the Institute of Cancer Research; Royal Marsden NHS Foundation Trust; Susan G. Komen for the Cure; Basser Center for BRCA; and the Breast Cancer Research Foundation.

The authors declare no conflicts of interest.