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Study: Ovary removal reduces risk of death from any cause in people with BRCA mutations

Summary

People who test positive for an inherited BRCA1 or BRCA2 mutation can reduce their risk of ovarian cancer by having both ovaries and fallopian tubes removed. A study published in 2024 found an added benefit of this surgery – a lower risk of death from any cause by age 75. (Posted 5/23/24)

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Ovary removal reduces risk of death from any cause in people with BRCA mutations

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RELEVANCE

Most relevant for: People who have had a risk reducing bilateral oophorectomy.
It may also be relevant for:

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

Relevance: High

Strength of Science: High

Research Timeline: Post Approval

Relevance Rating Details

What is this study about?

This study followed women with an inherited or mutation who had their ovaries removed. The researchers wanted to see if removal of ovaries to prevent ovarian cancer could also reduce the risk of death from any cause. The results confirm that removal of ovaries reduces death from any cause by age 75.

Why is this study important?

People with an inherited or mutation have an increased risk for cancer, including and ovarian cancer. There is currently no effective screening test for ovarian cancer. Currently, the most effective way to lower risk for ovarian cancer is with risk-reducing surgery to remove the ovaries and . Expert guidelines recommend that people with an inherited or mutation have their ovaries and removed between the ages 35 and 45 to decrease their risk of developing ovarian cancer. This study confirms that the removal of ovaries and in these women not only lowers cancer risk but lowers risk of death as well. This report is an update to a 2014 report that linked ovary removal to a 70 percent lower risk of death from any cause for this group.

Study findings

Women with high risk of ovarian cancer due to an in or who had their ovaries removed were less likely to die of any cause.

The study followed 4,332 women with and gene mutations who had both ovaries and tubes removed ( salpingo-oophorectomy) to prevent ovarian cancer. The important findings were:

Study participants who had their ovaries removed were 68% less likely to die by age 75.
Participants with an inherited mutation had a 72% lower risk of death.
Participants with an inherited mutation had a 57% lower risk of death.

In other words, women with a mutation who had surgery by age 35 were much less likely to die of any cause by age 75 (25% compared to 62%). This number dropped from 28% to 14% in women with a mutation.

About the study

Participants were part of a long-term international study of women with or mutations. Their average age was 42.6 years, and no participants had a personal history of cancer. The research team followed them for an average of nine years, some as many as 24 years. Participants were surveyed every two years either by mail or by phone. Information on death was gathered through patient records, doctors, or family members.

Out of the 4,332 participants, 2,932 women had their ovaries removed and 1,400 did not have their ovaries removed. A total of 228 deaths occurred, where 112 deaths were out of the 2,932 women who had their ovaries removed and 116 were out of the 1,400 women who did not have their ovaries removed. Most deaths (80 percent) were from cancer.

What does this mean for me?

If you have tested positive for an inherited or gene mutation, experts recommend having your ovaries and tubes removed to prevent cancer. It is well known that this surgery can help prevent ovarian and cancer and, the results of this study suggest removal of your ovaries also lowers your risk of dying of any cause by age 75.

The recommended age for this surgery is 35-40 for women with mutations and 40-45 for women with mutations and after childbearing is completed.

Ovary removal before natural menopause can have a number of affects. It increases the risk of heart disease and , affects fertility, bone health, and sexual health. It also can lead to lower quality of life. For these reasons, this procedure is only recommended to people with an inherited genetic mutation linked to cancer. Talk with your doctor about the risks and benefits of this procedure and suggested timing that is right for you.

Reference

Kotsopoulos J, Gronwald J, Huzarski T, et al., oophorectomy and all-cause mortality in women with and sequence variations. Journal of the American Medical Association Oncology; 2024; Article number 10.1001. Published online February 29, 2024

Trivedi M and Armstrong K, Increasing the uptake of cancer risk management strategies for women with BRCA1/2 sequence variations. Journal of the American Medical Association Oncology; 2024; Published online February 29, 2024 (accompany editorial to primary reference)

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 5/23/24

Questions To Ask Your Doctor

Do you recommend that I have my ovaries removed to prevent cancer?
What are the potential risks and benefits of this procedure?
When is the best time (at what age) to have this surgery?
What else can I do to lower my risk of cancer?

Guidelines

The National Comprehensive Cancer Network (NCCN) provides guidelines for management of gynecologic cancer risk in people with and mutations.

Prevention

Risk-reducing removal of ovaries and , (known as salpingo-oophorectomy) is recommended between ages 35-40 for and 40-45 for and upon completion of childbearing.
- Research studies show that removing the ovaries can increase survival for women with 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 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 and progesterone.
  - Adding progesterone to hormone replacement can protect against uterine cancer. However, the combination of these hormones may increase the risk for breast cancer more than 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 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 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 are ongoing. At this time whether 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. However, some doctors still recommend this screening, starting at ages 30-35.
Women should be aware of the symptoms of gynecologic cancer and report abnormalities to their doctors.

Updated: 05/08/2024

Open clinical trials

The following are studies looking at level of risk or risk-management for people with inherited or mutations. Check study listings or contact the study team to see if you are eligible.

Multiple cancers

NCT04367675: Testing a Vaccine for Cancer Prevention in People with a or Mutation. This study will look at a new vaccine known as INO-5401 used alone or combined with a second vaccine called INO-9012. The study will test if the vaccine is safe and if it activates the immune system. A goal of this research is to reduce cancer risk in people with a or mutation.
The Risk Factor Analysis of Hereditary Breast and Ovarian Cancer In Women with , or Mutations. This study seeks to improve researchers’ understanding of how hormonal, reproductive and lifestyle factors may be associated with cancer in this high-risk population.
Identification and Analysis of Families With Genetic Susceptibility To Cancer Registry. The research laboratory at the Abramson Cancer Center is studying genetic sources of cancer risk. A number of research projects are performed in collaboration with this registry.

Breast cancer

NCT04711109: Denosumab for Preventing Breast Cancer in Women with a Inherited Mutation (BRCA-P). This study will test the effectiveness of a drug (denosumab) on preventing the development of breast cancer in women with an inherited mutation.

cancer

NCT03805919: Men at High Genetic Risk for Cancer. This is a cancer screening study using in high risk men. This study is open to men with , and other inherited mutations.

Ovarian cancer

Validating a Blood Test for Early Ovarian Cancer Detection in High-risk Women and Families: MicroRNA Detection Study (MiDE). The goal of MiDe is to develop a test to detect ovarian cancer. Participants can be expected to provide up to 4 tubes of blood every 6 months for up to 5 years. We can collect these samples through mobile phlebotomy all around the US. The study is enrolling people with , and other mutations.
NCT04251052: A Study to Compare Two Surgical Procedures in Women with Mutations to Assess Reduced Risk of Ovarian Cancer (SOROCk). This study is looking at whether removal of just the can reduce the risk of ovarian cancer nearly as much as removing both the ovaries and among women with an inherited mutation.
NCT05287451: Risk Reducing With Delayed as an Alternative to Risk- Reducing Salpingo-oophorectomy in High Risk-Women to Assess the Safety of Prevention. This study will look at outcomes in women with , , , and who remove their first, followed by removal of their ovaries compared to women who undergo standard-of-care removal of their ovaries and at the same time.
NCT04794322: Developing a Test for the Detection of Ovarian Cancer. The study aims to develop a test for early detection of ovarian cancer using from a growth involving the ovary found in a washing of the uterus (womb), and proteins found in the blood. Participants will not receive the results of their test.

Pancreatic cancer

NCT03250078: A Pancreatic Cancer Screening Study in Hereditary High Risk Individuals. The main goal of this study is to screen and detect pancreatic cancer and precursor lesions in individuals with a strong family history or genetic predisposition to pancreatic cancer. and Magnetic cholangiopancreatography (MRI/MRCP) will be utilized to screen for early pancreatic lesions.
NCT02206360: Pancreatic Cancer Early Detection Program. This pancreatic cancer screening study uses esopheal to screen for pancreatic cancer in high risk people. The study is open to people who have a family history of pancreatic cancer and an in , or other genes.
NCT03568630: Blood Markers of Early Pancreas Cancer. This pancreatic cancer study involves blood samples over time to look for biomarkers of pancreatic cancer in high risk people. The study is open to people with a mutation linked to increased cancer risk.
NCT02478892: Preliminary Evaluation of Screening for Pancreatic Cancer in Patients with an Inherited Genetic Risk Due to a , , or Mutation. This study uses and endoscopic to screen for pancreatic cancer in people with a BRCA1/2, or mutation.

Additional risk-management clinical trials for people with inherited mutations may be found here.

Updated: 09/11/2022