Breast Cancer Gene Mutation Increases Risk of Aggressive Uterus Cancer, Study Reveals

Breast Cancer Gene Mutation Increases Risk of Aggressive Uterus Cancer, Study Reveals

A large study by the Duke Cancer Institute confirms that women who carry a mutation in the BRCA1 gene — a known risk factor for aggressive breast cancer — also risk developing a deadly cancer of the uterus.

The study, Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations, published in the journal JAMA Oncology, will likely change how women with the mutations are treated, offering women the choice to get their uterus removed to prevent cancer.

Having a mutation in the BRCA1 gene has been known as a risk factor for some time. Current research recommends that women with the faulty gene remove both breasts, and possibly their ovaries and fallopian tubes to prevent the cancer from developing in these high-risk organs.

While smaller studies have suggested that the uterus might be another organ worth removing to protect women from BRCA1-related cancer, the evidence had been weak and inconclusive.

“This is the study that has been needed,” said senior study author Noah D. Kauff, head of the Clinical Cancer Genetics Program at the Duke Cancer Institute. “Our study presents the strongest evidence to date that women with this genetic mutation should at least discuss with their doctors the option of having a hysterectomy (removal of the uterus, cervix and sometimes part of the vagina) along with the removal of their ovaries and fallopian tubes.”

The new study has examined enough people to be able to draw firm conclusions — 1,083 women from the U.S. and the United Kingdom were included. The women, having mutations in either the BRCA1 or BRCA2 genes, have had their ovaries and fallopian tubes removed.

The group was compared to rates of uterine cancer in the general population, numbers provided by the U.S. Surveillance, Epidemiology, and End Results program (SEER).

Among women with the BRCA mutations, with about half the women followed for three to 8.4 years, researchers recorded eight cases of uterine cancer, a number that is somewhat higher that other people, but is not statistically significant.

However, when researchers looked closer, they realized that five out of the eight cancers were of a particularly aggressive type, called serous endometrial cancer. This rare cancer hit four women with the BRCA1 mutation, and one carrying a BRCA2 variant.

Five cases among 1,083 women might not sound a lot, but compared to the rates seen in people without the mutation, the risk was significantly elevated.

“We were surprised when we saw the data,” Kauff said. “This is an event that should not occur in the over 600 women with BRCA1 mutations in our study. Even if we followed these women for 25 years, you would only expect to see no more than one serous cancer.”

Serous endometrial cancer kills about half the women who fall ill, but the researchers point out that it is possible to prevent it in women who plan to remove their ovaries and fallopian tubes, also including the uterus in the removed organs.

“Our findings suggest that it may be important for women with BRCA1 mutations to consider removing their uterus at the time they are considering removing their ovaries and fallopian tubes, unless they are hoping to still have children using assisted reproductive methods or have other medical reasons,” Kauff said.

The study does not answer how a uterus removal affects the risk in women who previously had their ovaries and fallopian tubes cut out.

“We need additional studies to address whether a 25-year risk of serous uterine cancer of 2.6 percent to 4.7 percent justifies the costs and potential complications of a second surgery,” Kauff said.