Study: Mutations in BRCA1 or BRCA2 may increase risk for endometrial cancer
A Dutch study added further evidence that women with a BRCA1 mutation may have an elevated risk for endometrial cancer. The study found that the endometrial cancer in women with either a BRCA1 or BRCA2 mutation was more likely to be an aggressive form of cancer associated with a poor outcomes. (posted 11/30/21)
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Contents
At a glance | Clinical trials |
Study findings | Guidelines |
Strengths and limitations | Questions for your doctor |
What does this mean for me? | Resources |
In-depth |
STUDY AT A GLANCE
What is this study about?
This study looked at whether women with an inherited 1 or mutation are at increased risk of developing endometrial cancer.
Why is this study important?
The exact risk for endometrial cancer in women with BRCA mutations is not clear. National guidelines recommend risk-reducing salpingo-oophorectomy (removal of the ovaries and ) for women with a or BRCA2 mutation. People with an inherited BRCA mutation should know their overall risk for endometrial cancer. When considering risk-reducing surgery to remove their ovaries and fallopian tubes, knowing their risk for endometrial cancer can help women decide whether to also remove their uterus at the same time.
Study findings
This study looked at the endometrial cancer risk between women with an inherited BRCA mutation who were enrolled in the Hereditary Breast and Ovarian study in the Netherlands as compared to two groups:
- The general population of Dutch women.
- Women without a BRCA mutation who had family members with a known BRCA mutation.
Among women whose family had a BRCA mutation, those who had the mutation and those who did not were followed for up to 27 years or until they died or were diagnosed with cancer.
Lifetime risk for developing endometrial cancer
This study showed that Dutch women with a BRCA1 or BRCA2 mutation had a slightly increased lifetime risk of endometrial cancer: 2.0-3.4 percent depending on the mutation compared to 1.0-1.4 percent among women in the general Dutch population. (Women in the US have 3 percent risk.)
Women who do not have their family’s known BRCA mutation are an excellent comparison group because they are expected to share many genetic and environmental features (more than with the general population).
- In this study, the lifetime risk of endometrial cancer for BRCA1 mutation carriers was 3.4 percent.
- Women with a BRCA1 mutation were more than three times more likely to develop endometrial cancer compared with women in the general Dutch population.
- Women with a BRCA1 mutation were also about three times more likely to develop endometrial cancer compared to women who did not have their family’s known BRCA1 mutation.
- In this study, the lifetime risk of endometrial cancer for BRCA2 mutation carriers was 2 percent.
- Women with a BRCA2 mutation were almost twice as likely to develop endometrial cancer than women in the general population. However, this result was barely significant (2.0% compared to 1.0-1.4%).
- In a more direct comparison, women with a BRCA2 mutation did not have an increased risk of endometrial cancer when compared to women without their family’s known BRCA2 mutation.
- This suggests that BRCA2 mutations may not increase endometrial cancer risk.
Type of endometrial cancer risk
Although the risks of developing endometrial cancer were low in women with a BRCA mutation, some differences were observed:
- Women with a BRCA mutation, especially those with a BRCA1 mutation, were more likely to be diagnosed with a more aggressive form of endometrial cancer called serous-like endometrial cancer compared with women in the general population.
- Women with an inherited BRCA1 mutation were more likely to develop serous-like endometrial cancer compared to women without their family’s known BRCA1 mutation (the better comparison group).
- Women with a BRCA2 mutation did not have a greater risk for any form of endometrial cancer compared to women known to not have a BRCA2 mutation.
Strengths and limitations
Strengths
- The study followed participants over a long period (average follow-up was 22.5 years), allowing researchers to evaluate long-term trends.
- This study compared people with BRCA mutations to family members without BRCA mutations. This is stronger than a comparison to the general population because the number of people with a mutation in BRCA1 or BRCA2 in the general population is unknown.
Limitations
- The study only looked at endometrial cancer risk in people with inherited BRCA1 and BRCA2 mutations. It did not look at inherited mutations in other genes that are known to increase cancer (e.g., , , , , ).
- The researchers did not have access to additional participant health information, including other risk factors for endometrial cancer, making it impossible to account for these factors in the analysis.
- The study only included women in the Netherlands. This limits its generalizability for women of other nationalities.
- When people had risk-reducing removal of ovaries and Fallopian tubes (), researchers did not know whether they also had a hysterectomy (uterus removal). Because people with RRSO and an intact uterus are still be at risk for endometrial cancer, they did not exclude anyone with an RRSO surgery (include anyone without a uterus and therefore much decreased risk of endometrial cancer). However, they note that hysterectomy is not commonly done with RRSO surgery in the Netherlands so this may not include many participants.
What does this mean for me?
Women with a BRCA1 or BRCA2 mutation who are considering risk-reducing salpingo-oophorectomy (RRSO) to remove their ovaries and fallopian tubes may also want to consider hysterectomy (removal of the uterus) at the same time. For women with a uterus, plus progesterone hormone therapy is recommended after risk-reducing removal of the ovaries and fallopian tubes. For pre-menopausal women, hormone replacement therapy has not been shown to increase the risk of breast cancer. However, there may be some risk for post-menopausal women. Removing the uterus allows for simplified hormone replacement therapy with estrogen alone, to avoid potential risk of breast cancer.
Although the lifetime risk for endometrial cancer is very low among individuals with BRCA mutations, some women whose risk is high due to personal risk factors or family history of endometrial cancer may choose to have risk-reducing hysterectomy.
Current guidelines recommend that women with an inherited BRCA mutation speak with their healthcare provider about the benefits and risks of hysterectomy at the time of risk-reducing salpingo-oophorectomy (removal of the ovaries and fallopian tubes). You can read more about the benefits and risks of these risk-reducing surgeries here.
If you have a BRCA mutation and you have had risk-reducing salpingo-oophorectomy but kept your uterus, you may still have increased risk for endometrial cancer. Currently, experts do not recommend hysterectomy to reduce endometrial cancer risk for women who did not remove their uterus at the time of their RRSO.
The most common sign of endometrial cancer is abnormal vaginal bleeding. Women who have additional risks, symptoms or concerns about endometrial cancer should speak with their surgeon about the benefits and risks of hysterectomy.
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posted 11/30/21
References
de Jong MM, de Kroon CD, Jenner DJ, et al. Endometrial cancer risk in women with BRCA1 or BRCA2 mutations: multicenter cohort study. Journal of the National Cancer Institute; 2021; 113 (9): djab036. Published online March 12, 2021.
Sherman ME, Foulkes WD. BRCA1/2 and endometrial cancer risk: implications for management. Journal of the National Cancer Institute; 2021; 113 (9): djab037. Published online March 12, 2021.
Nahshon C, Lavie O. RE: Endometrial cancer risk in women with germline BRCA1 or BRCA2 mutations: multicenter cohort study. Journal of the National Cancer Institute; 2021; 00 (0): djab154. Published online August 23, 2021.
de Kroon CD, de Jonge MM, Bosse T, van Asperen CJ. Response to Nahshon and Lavie. Journal of the National Cancer Institute; 2021; 00 (0): djab155. Published online August 23, 2021.
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.
The National Comprehensive Cancer Network (NCCN) provides guidelines for the management of gynecologic cancer risk in people with BRCA1 and BRCA2 mutations.
Prevention
- Risk-reducing removal of ovaries and fallopian tubes, (known as risk-reducing salpingo-oophorectomy or RRSO) is recommended between ages 35-40 for BRCA1 and 40-45 for BRCA2 and upon completion of childbearing.
- Research shows that removing the ovaries can increase survival for women with BRCA1 or BRCA2 mutations.
- Women should talk with their doctors about the effects of early menopause and options for managing them.
- Women should talk with their doctors about the risks and benefits of keeping or removing their uterus (hysterectomy), including:
- Women with a BRCA1 or BRCA2 mutation have an increased risk for a rare form of aggressive uterine cancer; hysterectomy removes this risk.
- For women considering hormone replacement after surgery, the presence or absence of a uterus can affect the choice of hormones used.
- Estrogen-only hormone replacement is less likely to increase the risk for breast cancer, although it increases the risk for uterine cancer. Women who still have their uterus are typically given hormone replacement with both estrogen and progesterone.
- Adding progesterone to estrogen hormone replacement can protect against uterine cancer. However, the combination of these hormones may increase the risk for breast cancer more than estrogen alone.
- A medical history of fibroids or other uterine or cervical issues may justify a hysterectomy.
- Oral contraceptives (birth control pills) have been shown to lower the risk for ovarian cancer in women with BRCA mutations. Research on the effect of oral contraceptives on breast cancer risk has been mixed. Women should discuss the benefits and risks of oral contraceptives for lowering ovarian cancer risk with their doctors.
- Removal of the fallopian tubes only () is being studied as an option for lowering risk in high-risk women who are not ready to remove their ovaries. Studies on the effects of salpingectomy are ongoing. Whether salpingectomy lowers the risk for ovarian cancer in high-risk women remains unknown.
- Consider enrolling in a research study looking at this procedure to lower cancer risk.
Screening
- There are no proven benefits to routine ovarian cancer screening using transvaginal and a blood test. These tests are not currently recommended.
- After RRSO, a very small risk remains for a related cancer known as primary peritoneal cancer (PPC). There is no effective screening for PPC after RRSO
- Women should be aware of the symptoms of gynecologic cancer and report abnormalities to their doctors, particularly if they persist for several weeks and are a change from normal. These symptoms can include:
- pelvic or abdominal pain
- bloating or distended belly
- difficulty eating
- feeling full sooner than normal
- increased urination or pressure to urinate
Updated: 01/29/2025
- How can I reduce my risk of endometrial cancer?
- What are the signs of endometrial cancer?
- I have a personal history of breast or ovarian cancer. Am I at greater risk for endometrial cancer?
- I have a diagnosis of endometrial cancer. Do I need to be tested for an inherited BRCA mutation?
- I have an inherited BRCA mutation. Should I be screened for endometrial cancer?
The following organizations offer peer support services for people with or at high risk for endometrial cancer:
- FORCE peer support
- Our Message Boards allow people to connect with others who share their situation. Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Private Facebook Group.
- Virtual and in-person support meetings.
- Join a Zoom community group meeting.
- SHARE is a nonprofit that provides support and information for women with breast, ovarian or endometrial cancer.
-
ECANA is an online resource for Black people with endometrial cancer.
Updated: 08/28/2022