Study: Study: Endometrial cancer risk for people with BRCA1 and BRCA2 mutations

RELEVANCE

Most relevant for: Women with a BRCA1 or BRCA2 mutation who have a uterus..

It may also be relevant for:

• people with breast cancer
• people with ovarian cancer
• previvors
• people with a genetic mutation linked to cancer risk
• people with a family history of cancer

Relevance: Medium-High

Strength of Science: Medium-High

Research Timeline: Post Approval

More rating details

What is this study about?

Inherited BRCA1 and BRCA2 mutations are known to increase the risk of breast and ovarian cancers. Less is known about whether these mutations also increase the risk of endometrial cancer, which occurs in the lining of the uterus. This study followed nearly 5,000 people with BRCA mutations over an average of nearly seven years to better understand the risk of endometrial cancer.

Why is this study important?

Previous research found that people with inherited BRCA mutations may have a slightly higher risk for endometrial cancer (including serous endometrial cancer that is more aggressive) than people without BRCA gene mutations. However, not all studies have linked BRCA mutations to endometrial cancer. While risk-reduction surgery to remove the fallopian tubes (salpingectomy) and ovaries (oophorectomy) is recommended for people with BRCA mutations, national guidelines recommend that surgery to remove the uterus (hysterectomy) should be discussed and tailored to a person's personal and family medical history. Accurate information on the risk of endometrial cancer in people with BRCA mutations can better inform medical decisions, including whether a risk-reducing hysterectomy is the best option for the person having surgery.

Study findings

This study followed 4,959 people with BRCA mutations: 3,454 had a BRCA1 mutation and 1,505 had a BRCA2 mutation:

• 38 of 4,959 (0.7%) were diagnosed with endometrial cancer during this study, including:
  • 30 with a BRCA1 mutation (1%)
  •  8 with a BRCA2 mutation (0.5%)
• The average age at diagnosis was 58 years.

The researchers focused on answering the following questions to better understand the risk of endometrial cancer in people with BRCA mutations.

Is the risk of endometrial cancer increased among people with a BRCA mutation compared to people without a BRCA mutation?
To answer this question, the researchers compared the number of study participants they expected to be diagnosed with endometrial cancer during the study based on the historical rate of endometrial cancer in the general public for a group of this size.

BRCA1: More people than expected had endometrial cancer during the follow-up period, especially younger people. This indicates an increased risk of endometrial cancer for younger people with BRCA1 mutations. However, the lifetime risk was estimated to be similar to people without mutations.

BRCA2: People with BRCA2 mutations had endometrial cancer at a rate similar to people without mutations.

What is the estimated lifetime risk of endometrial cancer among people with BRCA1 or BRCA2 mutations?
The researchers estimated that by age 70, in those who have a uterus:

• people with a BRCA1 mutation have a 3.4% risk of endometrial cancer.
• people with a BRCA2 mutation have a 1.6% risk of endometrial cancer.*
• people without a BRCA mutation have a 3.0% risk of endometrial cancer.
  
  People with a BRCA1 mutation may have a slightly increased risk of endometrial cancer compared to people without a BRCA mutation; however, in this study, people with a BRCA2 mutation did not appear to have an increased risk.
  
  *Please note: These results do not mean that having a BRCA2 mutation protects against endometrial cancer. Experts believe the lifetime risk among people with BRCA2 mutations is similar to people without mutations.

Are other factors that impact endometrial cancer more likely to affect people with BRCA mutations?

Factors that are known to increase the risk for endometrial cancer include age, tamoxifen use and obesity.

 In this study:

• Women aged 50 and older or women who had taken tamoxifen were more likely to be diagnosed with endometrial cancer.
  • Of the 38 people with endometrial cancer, only 3 were under age 50 when diagnosed.
  • 12 of the 38 people with endometrial cancer had a history of taking tamoxifen to prevent or treat breast cancer.
  • Past tamoxifen use was associated with a 2-fold increase in endometrial cancer risk.

• No link was found in this study between endometrial cancer and prior oophorectomy, hormone use (such as hormone replacement therapy after oophorectomy), smoking or body mass index (an indicator of obesity).

What does this mean for me?

If you have an inherited BRCA1 or BRCA2 mutation, results from this study indicate that your overall risk of endometrial cancer is low. Younger BRCA1 carriers were more likely to get endometrial cancer than those without mutations, but their estimated lifetime risk was similar.

People with BRCA1 or BRCA2 mutations who are making decisions about hysterectomy should discuss with their surgeon the factors that may affect their decisions, including:

Risk for endometrial cancer

• Prior research has shown an increased risk for a rare type of aggressive endometrial cancer in people with BRCA1 mutations. The overall lifetime risk is small: about 3%.  

Decisions about hormone replacement

• For people who plan to take hormones after risk-reducing ovary removal, removing the uterus may alter how hormone replacement is given.
  • People who keep their uterus are recommended to have a combination of estrogen and progesterone hormone replacement to protect against endometrial cancer.
  • People who have a hysterectomy can take estrogen-only hormone replacement.

Decisions about surgery and recovery

• Adding hysterectomy to risk-reducing ovary removal slightly increases the risk for surgical complications, including bleeding, infection, the need for more extensive surgery and increased recovery time.

Previous uterine or cervical abnormality

• Hysterectomy is often considered for people who have had abnormal pap smears or an abnormality of the uterus.

Reference

Kotsopoulos J, Lubinski J, Huzarski T, et al. Incidence of endometrial cancer in BRCA mutation carriers. Gynecologic Oncology. 2024; 189:148-155.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 10/7/25