Women with BRCA1 mutations may have increased risk for rare types of aggressive uterine cancer

Women with BRCA1 mutations may have an increased risk for developing rare types of aggressive uterine cancer despite having their ovaries and fallopian tubes removed, suggest preliminary findings being presented at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women's Cancer in Tampa, Fla., March 22-25.

Women with mutations in the BRCA1 gene who are considering having their ovaries and fallopian tubes removed to reduce the risk of both gynecologic and breast cancers, a procedure called risk-reducing salpingo-oophorectomy (RRSO), should discuss with their physicians the potential advantages and disadvantages of also having a hysterectomy (removal of the uterus) during the same procedure, suggest researchers. However, because this is one of the first studies to report these findings, the results need to be confirmed before hysterectomy should be routinely recommended, they note.

The study from Memorial Sloan Kettering Cancer Center in New York focused on 525 women with BRCA1 or BRCA2 mutations who had RRSO without a hysterectomy to prevent the development of both gynecologic and breast cancers. This represented 79 percent of women undergoing risk-reducing surgery during the study period. Four of the 296 women with a BRCA1 mutation who did not have the uterus removed subsequently developed an aggressive form of uterine cancer. That translates into a 2.1 percent risk of developing an aggressive uterine cancer in the first 10 years following RRSO. This is approximately a 26-fold increased risk compared to what would be expected in the general population. Importantly, there was no increased risk found for the more common types of uterine cancer, and the increased risk of aggressive uterine cancer may have been associated with a prior history of breast cancer and/or use of tamoxifen, a breast cancer treatment.

In the study, 296 of the 525 women (56 percent) had a BRCA1 mutation, 226 (43 percent) had a BRCA2 mutation and three (.6 percent) had mutations in both genes. None of the women with a BRCA2 mutation developed uterine cancer. Researchers are continuing to study whether women with the BRCA2 mutation also are at higher risk for rare types of uterine cancer.

"While the absolute risk is still relatively low, it is much higher than we would have expected for these aggressive uterine cancers," said Noah D. Kauff, MD, senior author of the study and director of ovarian cancer screening and prevention on the gynecology service at Memorial Sloan Kettering. "Doctors should let their patients with BRCA1 mutations know that this report suggests they may be at risk for rare types of aggressive uterine cancer. However, whether or not a woman decides to have a hysterectomy at time of risk-reducing salpingo-oophorectomy may depend on her age, prior cancer history and other risk factors."

Women with a BRCA1 mutation have a 39 to 46 percent chance of developing ovarian cancer and a 50 to 85 percent chance of developing breast cancer in their lifetimes. Because of the high risk of developing those cancers, the National Comprehensive Cancer Network currently recommends that women with a BRCA1 mutation reduce their risk of developing both ovarian and breast cancer by having their ovaries and fallopian tubes removed between age 35 and 40 after childbearing is complete. The recommendation doesn't include removal of the uterus because there are extra risks to undergoing a hysterectomy, including higher risks of bleeding and infection, and potentially higher risks of long-term problems with bladder, bowel or sexual function. It also was believed that uterine cancers that do develop following RRSO were likely to be low risk. The new study suggests that may not be the case.


Society of Gynecologic Oncology 


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