Study: Hormone therapy and breast cancer risk after ovary removal in women with a BRCA1 mutation
Summary
Does hormone therapy (HT) alter the risk of breast cancer for woman carrying a BRCA1 mutation who have never been diagnosed with cancer? In this study, researchers showed that among women with BRCA1 mutations, HT use did not increase breast cancer rates for 10 years after ovary removal. More women taking combined estrogen plus progesterone developed breast cancer compared to those taking estrogen only, though this difference was not statistically significant. (9/7/18)
Relevance
This article is most relevant for Women with BRCA1 mutations who have had risk-reducing ovary removal and have never been diagnosed with breast cancer
Relevance: Medium-High
Strength of Science: High
Research Timeline: Post Approval
Media Ratings
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Who covered this study?
Healio
Estrogen after oophorectomy does not increase breast cancer risk.
This article rates 2.5 out of 5 stars
Cancer Therapy Advisor
Post-oophorectomy estrogen therapy may not Increase breast cancer risk in BRCA1 carriers
This article rates 2.5 out of 5 stars
Contents
| At a glance | Media coverage |
| Findings | In-depth |
| Clinical trials | Limitation |
| Questions for your doctor | Resources |
STUDY AT A GLANCE
This study is about:
Whether hormone therapy (HT) started after removal of the ovaries is associated with increased breast cancer risk among women with mutations who have never been diagnosed with cancer.
Why is this study important?
HT alleviates symptoms of menopause associated with removal of the ovaries (). Although review of medical records show that HT does not appear to change the risk of breast cancer for women with mutations who had their ovaries removed, no study has examined this issue. Knowing how HTs affect breast cancer risk may be helpful for decision making by women with mutations.
Study findings:
This study followed 872 women with mutations who had risk-reducing . Among these women, 43% chose to use HTs and 57% did not. During the study period, 92 (10.6%) of the participants were diagnosed with breast cancer:
- There was no increase in breast cancer between those who used HT compared to those who did not.
- The rate of breast cancer differed by the type of HT used:
- 12% of women who used estrogen-only HT were diagnosed with breast cancer.
- 22% of women who used progesterone-estrogen combination HTs were diagnosed with breast cancer.
- While this difference was seen, it did not reach statistical significance. However, the number of women taking progesterone-estrogen HT was small, so subtle differences may be undetectable.
- Of note, this study suggests that alone could be associated with some benefit. For every year on estrogen-only HT, there was a relative reduction of risk compared to women who took no hormones. This same protective effect was not seen in the estrogen-progesterone combination HT. More research is needed to determine the long term benefits of estrogen-only HT.
What does this mean for me?
National guidelines recommend that all women with a mutation have their ovaries and removed between the ages of 35-40 to lower their risk for ovarian cancer. If you are a previvor who has had or will have your ovaries removed, this study showed that using hormone replacement therapy for 10 years will not increase your risk of breast cancer.
Although not statistically significant, breast cancer rates were higher in women who took HT that contains progesterone compared with women who took estrogen-only HT. It’s important to note that estrogen-only HT can increase the risk for uterine cancer. Progesterone is often given to women who have had risk-reducing ovary removal but who have not removed their uterus. Progesterone can lower the risk for uterine cancer in women who take . Women who are planning risk-reducing removal of their ovaries should speak with their health care provider about whether or not they should remove their uterus at the time of surgery.
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Posted 9/7/18
References
Kotsopoulos J, Gronwald J, Karlan BY, et al. "Hormone replacement therapy after and breast cancer risk among mutation carriers." JAMA Oncology. 2018. 4(8):1059-1065. doi:10.1001/jamaoncol.2018.0211.
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.
This article is relevant for:
Women with BRCA1 mutations who have had risk-reducing ovary removal and have never been diagnosed with breast cancer
This article is also relevant for:
previvors
people with a genetic mutation linked to cancer risk
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IN-DEPTH REVIEW OF RESEARCH
Study background:
Women with mutations have a greater risk of ovarian and breast cancers: about 44% risk of ovarian cancer and 72% risk of breast cancer by age 80. The ovaries are a natural source of and progesterone; risk-reducing removal of the ovaries () and reduces the risk of ovarian cancer by 80%, but also causes surgical menopause. To reduce menopause symptoms, some women elect to use hormone therapy (HT). HT usually contains and/or progesterone.
How HT use affects breast cancer risk in women with and mutations has been unclear. Several studies have shown contradictory results among women in the general population who took hormones after natural menopause. In the Women's Health Initiative (WHI)—a very well designed and large study—women using progesterone plus (versus ) had increased rates of breast cancer and heart disease. The estrogen-only group of the WHI had an increased risk of stroke but a decreased risk of breast cancer.
The researchers of this study showed in a prior case-control study that women with mutations who used HT did not have an increase in breast cancer rates. Here they conduct a study following 872 women with mutations who had risk-reducing removal of their ovaries.
Researchers of this study wanted to know:
Whether hormone therapy (HT) started after removal of the ovaries increases breast cancer risk among women with mutations who have never been diagnosed with cancer.
Populations looked at in this study:
Participants in this study were women from over 80 centers in 17 countries who have mutations and had oophorectomies (both ovaries removed). Women were excluded if they had a prior cancer, did not have a oophorectomy during the study period, had mastectomy (breast removal) during the study period or did not complete survey questionnaires.
Study findings:
This study followed 872 women with mutations who had had risk-reducing ovary removal (). Participants filled out questionnaires every 2 years about their history of cancer, reproductive and medical history, and HT use.
- Among the 872 women with mutations, 43% chose to use HTs after ovary removal and 57% did not.
Participants were asked if they had been diagnosed with invasive breast cancer. Study researchers looked at whether the women who reported a breast cancer diagnosis had used HTs or not.
- 10.9% (92 women of all participants) had been diagnosed with breast cancer.
No statistical difference in breast cancer rates was found between women who did or did not use HTs. This indicates that HT use in general is not associated with increased breast cancer risk.
- 10.3% of women who used HTs were diagnosed with breast cancer.
- 10.7% of women who did not use HTs were diagnosed with breast cancer.
Researchers looked at the type of HT used by women. The rate of breast cancer differed by the type of HT used. This difference was greater for women who had ovary removal before age 45.
- 12% of women who used estrogen-only HT were diagnosed with breast cancer.
- 22% of women who used progesterone-estrogen combination HTs were diagnosed with breast cancer.
- While this difference was seen, it did not reach statistical significance. Only 66 women used progesterone-estrogen combination HTs. Because the number of women taking progesterone-estrogen HT was small, subtle differences may be undetectable.
- The potential benefit of estrogen-only HT over plus progesterone HT needs further study.
- Of note, breast cancer risk was reduced by 8% for each year of estrogen-only HT use (for example, a 10.6% baseline risk would be reduced to 9.7% after one year of only HT use and 8.9% in 2 years of only HT use).
Limitations:
One limitation of this study is that the data came from self-reported questionnaires. However, researchers pointed out that prior studies suggest self-reported and medical records generally correspond.
This study assessed breast cancer rates for a 10-year period after ovary removal. It is unknown what results would be for HT use for longer periods of time.
This study examined the risk of breast cancer associated with HT use after ovary removal only for women with mutations. Women with mutations and other mutations are at high risk for breast and ovarian cancer as well. Researchers recruited women with mutations for this study but too few participants with were available to reach any direct conclusions. Whether results would be similar for women with mutations or other breast cancer predisposing mutations is an important question that is not addressed by this study. Because women with mutations, like women with mutations, often have hormone receptor-positive tumors, study researchers speculate that the results may be similar. This idea needs to be tested in future studies.
The impact of HTs on women who have not removed their ovaries was not examined; only women who had undergone risk-reducing ovarian removal were evaluated. However, a case-control study by the same researchers previously showed that women with mutations without ovary removal who took HTs did not have increased rates of breast cancer as compared to women with mutations without ovary removal who did not take HTs.
The differences in breast cancer rates among women who used different types of HTs indicated that estrogen-only HT use may be beneficial. It is possible that estrogen-progesterone HTs may be detrimental (based on trends in this study and data in other studies). However, not enough study participants used estrogen-progesterone HTs to adequately assess this specific HT.
Conclusions:
If you are a who has had or will have ovarian removal, this study suggests that your risk of breast cancer is not increased if you choose to use hormone replacement therapy. Estrogen-only HT is associated with less breast cancer risk than HT which contains progesterone.
Share your thoughts on this XRAYS article by taking our brief survey.
Posted 9/7/18
Expert 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
Expert Guidelines
The National Comprehensive Cancer Network (NCCN) provides the following guidelines for the management of gynecologic cancer risk in people with inherited mutations that are linked to endometrial or ovarian cancer. We recommend that you speak with a genetics expert who can look at your personal and family history of cancer and help you to determine the best risk management plan.
, or mutation
- Recommend risk-reducing salpingo-oophorectomy between the ages of 45-50.
- Be aware of endometrial and ovarian cancer symptoms.
- Consider endometrial biopsy every 1-2 years beginning at ages 30-35.
- For postmenopausal women, consider transvaginal after discussion with your doctor.
- Consider risk-reducing hysterectomy; discuss risk-reducing removal of ovaries and with your doctor (, , and ).
- Discuss the benefits and risks of oral contraceptives.
mutation
- Be aware of endometrial cancer symptoms.
- Consider endometrial biopsy every 1-2 years beginning at age 35.
- For postmenopausal women, consider transvaginal after a discussion with your doctor.
- Consider risk-reducing hysterectomy.
Updated: 02/23/2023
Expert Guidelines
National Comprehensive Cancer Network (NCCN) has cancer risk management guidelines for people with inherited mutations linked to cancer. In their guidelines on risk management for women at high risk for ovarian cancer, the NCCN panel states:
- Some research shows that hormone replacement after does not negate the reduction in breast cancer risk associated with the surgery. However, they caution those considering hormone replacement to consider the limitations of the existing research when making this decision.
- Individuals who undergo hysterectomy at the time of are candidates for estrogen-only hormone replacement therapy, which has been associated with a lower risk for breast cancer compared with combined and progesterone therapy. Individuals with an intact uterus are not candidates for estrogen-only therapy due to the increased risk of endometrial cancer.
The North American Menopause Society is a professional society of experts in the field of menopause.
- In 2017, the organization released a position statement on hormones replacement therapy, which includes the following:
- Menopause symptoms and a variety of diseases are more likely to occur in women who have surgical menopause from ovary removal. These symptoms can have a major effect on quality of life and potential adverse effects on the cardiovascular system, bone, mood, sexual health and cognition, which have been shown in observational studies to be lessened by therapy.
- Unless contraindications are present, therapy is indicated for women who have removed both ovaries to reduce their risk of sexual side effects, bone loss, heart disease and decline. For women who retain their uterus, endometrial protection (progesterone) is indicated.
- Specific to women with or mutations who have removed their ovaries to lower their risk for cancer:
- For women with or mutations who have not been diagnosed with breast cancer, some evidence suggests that that hormone therapy use after does not further increase the risk for breast cancer.
- Considerations should be made regarding the benefits of to prevent health risks caused by surgical menopause.
- Considerations should be made (based on a limited amount of data) about hormone therapy until age 52 with discussions about longer use based on the individual patient.
- In 2018, the organization released a joint position statement with the International Society for the Study of Women's Sexual Health regarding management of genitourinary syndrome of menopause (GSM) in women who have or at high risk for breast cancer, including the following:
- People with, or at high risk for breast cancer should discuss treatment options for GSM with their healthcare providers using a shared decision-making approach.
- For women diagnosed with breast cancer:
- Vaginal moisturizers and lubricants are recommended as initial treatment options.
- Local (vaginal) hormone treatment may be considered for women for whom nonhormonal options do not work. Local therapy should be individualized, taking into account the risk of disease recurrence and severity of vaginal symptoms.
- Intravaginal estrogens in women on tamoxifen may be less of a concern than intravaginal estrogens in women on aromatase inhibitors.
- For high-risk women without breast cancer who have undergone , vaginal hormone therapy is likely to be safe.
Updated: 08/13/2024
Questions To Ask Your Doctor
- Should I consider using HT after risk-reducing ovary removal? After menopause?
- What kind of HT would be most appropriate for me?
- What are other options for managing menopause without HT?
- What risks are associated with taking or not taking HT after removal of my ovaries?
- Can you refer me to a menopause expert?
Open Clinical Trials
The following studies of menopause and menopause management are for survivors and previvors.
- NCT04439370: Autonomic Regulation of Blood Pressure in Premature and Early Menopausal Women. This research studies how early menopause effects blood pressure.
- NCT03572153: A Mind-Body Intervention for Hot Flash Management. The main goal of this study is to test whether self-administered hypnosis can reduce hot flashes more effectively than self-administered white noise hypnosis over 6 weeks of home practice.
- NCT04821141: Phase IIB Trial of Bazedoxifene Plus Conjugated Estrogens. Women at increased risk for breast cancer who experience hot flashes will receive either bazedoxifene plus conjugated estrogens (similar to the drug Duavee) for 6 months or a control (no drug). Researchers will measure breast density with and needle biopsy that identifies biomarkers.
- NCT06112756: A Study to Learn About How Elinzanetant Works and How Safe it is in Women Having Sleep Disturbances Associated with Menopause (NIRVANA). This study looks at treatment the safety and efficacy of treatment with Elinzanetant for symptoms like hot flashes caused by hormonal changes associated with menopause that can impact sleep disturbances.
Updated: 02/03/2024
Peer Support
FORCE offers many peer support programs for people with inherited mutations.
- Our Message Boards allow people to connect with others who share their situation. Once registered, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Our Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Our moderated, private Facebook group allows you to connect with other community members 24/7.
- Check out our virtual and in-person support meeting calendar.
- Join one of our Zoom community group meetings.
Updated: 08/06/2022
Find Experts
The following resources can help you locate an expert near you or via telehealth.
Finding menopause experts
- The Menopause Society has a tool to help you find a qualified menopause expert in your area.
Related experts
Some symptoms of menopause may be managed by other experts. People experiencing menopause symptoms may benefit from a consultation with the following experts.
Sexual health experts
- The Sexual Medicine Society of North America has a search tool to find experts in your area who provide sexual health care services.
- The American Association of Sexuality Educators, Counselors and Therapists maintains a tool to help people find a sexual health expert near them.
Acupuncture experts
- The National Certification Commission for Acupuncture and Oriental Medicine has a searchable directory of licensed acupuncturists.
Sleep experts
- The American Academy of Sleep Medicine maintains the public-facing website SleepEducation.org which includes a section on finding a sleep center by location.
Bone density experts
- The Bone Health and Foundation has a searchable database for finding experts.
Other ways to find experts
- Register for the FORCE Message Boards and post on the Find a Specialist board to connect with other people who share your situation.
- National Cancer Institute (NCI)-designated comprehensive cancer centers have specialists to manage the symptoms and side effects of cancer prevention or treatment.
Updated: 09/11/2024
Related Resources
The following organizations have resources related to menopause for survivors and previvors.
- FORCE related resources:
- Information: Menopause
- XRAY category: Menopause
- FORCE video: Early menopause management for women who cannot take therapy (from 2022 conference)
- FORCE video: Menopause Management without Hormones (from 2021 conference)
- FORCE video: Early Onset Menopause Management with Hormones (from 2021 conference)
- FORCE video: Menopause Question-and-Answer Panel (from 2021 conference)
- FORCE video: Things you can do to optimize your sleep, starting tonight
- FORCE video playlist: Menopause (9 videos)
- The North Menopause Society is a professional organization devoted to promoting women's health and quality-of-life through an understanding of menopause. They certify providers who have passed an examination and maintained ongoing education related to menopause.
- The National Institutes of Health () and Related Bone Diseases National Resource Center has resources related to including sections specifically for people diagnosed with different types of cancer.
Updated: 09/12/2024
Who covered this study?
Healio
Estrogen after oophorectomy does not increase breast cancer risk.
This article rates 2.5 out of 5 stars
Cancer Therapy Advisor
Post-oophorectomy estrogen therapy may not Increase breast cancer risk in BRCA1 carriers
This article rates 2.5 out of 5 stars