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BRCA1 Mutation Linked to Higher Risk of Specific Type of Uterine Cancer

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Most inherited cases of breast cancer are associated with mutations in two genes: BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two). It’s been estimated that women with a BRCA1 or BRCA2 genetic mutation have up to a 72% risk of developing breast cancer by age 80. These women’s risk of ovarian cancer also is higher than average. But because not much research had been done, it wasn’t clear if there were a link between having a BRCA1 or BRCA2 mutation and a higher risk of uterine cancer.

A study strongly suggests that women with a BRCA1 mutation have a slightly higher risk of serous or serous-like endometrial cancer, an uncommon but aggressive type of uterine cancer.

The research was published online on June 30, 2016 by JAMA Oncology. Read “Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations.”

If you know you have a BRCA1 or BRCA2 mutation, there are steps you can take to keep your risk as low as it can be. Protective or “prophylactic” surgery to remove the healthy breasts and ovaries are very aggressive risk-reducing options that some women with BRCA1 or BRCA2 mutations choose.

Prophylactic mastectomy reduces the risk of developing breast cancer by more than 90%. Removing both the ovaries and fallopian tubes, called “bilateral salpingo-oophorectomy,” by age 40 reduces breast cancer risk by 50%.

Doctors have been unsure if also removing a woman’s uterus -- this surgery is called a hysterectomy -- should also be recommended. Results from small studies looking for a link between a BRCA1 or BRCA2 mutation and uterine cancer offered conflicting results.

So researchers from nine institutions in the United States and the United Kingdom conducted a larger study to look for a link between a BRCA mutation and uterine cancer. Professional Advisory Board members Mary Daly, M.D. of the Fox Chase Cancer Center and Patricia Ganz, M.D. of the UCLA Jonsson Comprehensive Cancer Center were two of the paper’s authors.

The study included 1,083 women with a BRCA1 or BRCA2 mutation who had not been diagnosed with breast cancer and who had bilateral salpingo-oophorectomy between 1995 and 2011. None of the women had a hysterectomy.

  • 627 women had a BRCA1 mutation
  • 453 women had a BRCA2 mutation
  • 3 women had both a BRCA1 and a BRCA2 mutation

The women’s ages ranged from 41 to 52.5 years.

The women were followed for 3 to 13 years after surgery or BRCA testing, whichever happened last.

The researchers compared how many uterine cancers were diagnosed in the women in the study to rates of uterine cancer in the general population.

During follow-up, eight women were diagnosed with uterine cancer. This was slightly higher than what would be expected in the general population. Still, this slight increase was not statistically significant, which means that it could have been due to chance and not because the women had a BRCA mutation.

But of the eight uterine cancers, five were an uncommon subtype called serous or serous-like endometrial cancer, which is especially aggressive. Four of these aggressive endometrial cancers were diagnosed in women with a BRCA1 mutation. The other aggressive endometrial cancer was diagnosed in a woman with a BRCA2 mutation.

Based on the rates of serous or serous-like endometrial cancer in the general population, the researchers expected to find only about 0.18 cases of it among women with a BRCA1 mutation in the study. This difference was statistically significant, which means that it was likely because the women had a BRCA1 mutation and not just due to chance.

"We were surprised when we saw the data," said Noah Kauff, M.D. of the Clinical Cancer Genetics Program at the Duke Cancer Institute who was the lead author of the paper. "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.

"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," Dr. Kauff continued.

He cautioned that for women with BRCA1 mutations who have already had bilateral salpingo-oophorectomy, the results are less clear.

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

If you know you have a BRCA1 mutation and are considering protective surgeries to reduce your risk of breast and ovarian cancer, you may want to talk to you doctor about this study and what it means for your unique situation. If you’ve already had your ovaries and fallopian tubes removed, you might want to talk to your doctor about your personal risk of uterine cancer and whether having a hysterectomy makes sense for you.

Prophylactic surgery decisions require a great deal of thought, patience, and discussion with your doctors, genetic counselor, and family over time -- together with a tremendous amount of courage. Take the time you need to consider these options and make decisions that feel comfortable to you.

For more information, visit the Prophylactic Ovary Removal page.

Editor’s Note: This article was updated on Jan. 24, 2019, with updated information on cancer risk associated with BRCA mutations.

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