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Hormone Replacement Therapy After Menopause and Breast Cancer Risk

Posted on December 15, 2021
Medically reviewed by
Mark Levin, M.D.
Article written by
Elizabeth Wartella, M.P.H.

Hormone replacement therapy (HRT), also called menopausal hormone therapy (MHT), is a treatment used for menopausal symptoms such as hot flashes, night sweats, and insomnia. While there are benefits of using HRT, different types of HRTs may also produce some health risks. Among these risks is an increased risk of breast cancer, particularly from HRT that includes both estrogen and progestin.

The association between HRT and the risk of breast cancer was first discovered in a randomized clinical trial called the Women’s Health Initiative (WHI) in 2002. This study explored the health effects of two types of HRT in postmenopausal women: estrogen-only HRT, and HRT that contained a combination of progestin and estrogen. The trials were concluded early because participants taking the combined pill showed a significantly increased risk of breast cancer during a study follow-up.

Since the WHI trial, many other studies have explored the link between HRT and breast cancer risk. Research has found that the risk of breast cancer with HRT use depends on factors such as the type of HRT you follow, how long you do so, your body mass index, and your breast density. Progesterone-based HRTs are safer than those that are estrogen-based.

If you undertake HRT, the increased risk doesn’t mean that you will definitely develop breast cancer. The decision to take HRT is personal. It often depends on the severity of your menopausal symptoms and whether you have other genetic and lifestyle factors that increase your risk of breast cancer. If you are not a good candidate for HRT or are concerned about the risks, there are other tools that can help you address your menopausal symptoms.

How Does HRT Increase the Risk of Breast Cancer?

The development of breast cancer is influenced by a combination of factors that cause genetic mutations in the cells in a person’s breast. The mutations trigger your cells to multiply in unpredictable ways and lump together, creating cancerous tumors.

Both hereditary and environmental factors, including age, obesity, alcohol consumption, and a family history of breast cancer, can play a role in your potential development of breast cancer. Post-menopausal systemic HRT is considered one of these risk factors. While studies have explored the connection between HRT and breast cancer, researchers still don’t fully understand exactly how taking estrogen-only or estrogen plus progestin HRTs increases a person’s risk of breast cancer.

Estrogen and Breast Cancer

Estrogen is a naturally occurring hormone produced in your ovaries. It plays a role in your sexual and reproductive development. When you reach menopause, your production of estrogen slows down. One method of HRT includes supplementing that lost estrogen with estrogen in the form of a pill, patch, or vaginal suppository in order to help ease your menopausal symptoms. Estrogen-only HRT is typically only recommended if you have had a hysterectomy.

The Women’s Health Initiative study from 2002 actually found that participants who took the estrogen-only pill experienced a slightly decreased risk of breast cancer compared to those who took a placebo sugar pill.

Other research studies have found conflicting results. A 2009 meta-analysis that reviewed existing research noted several theories about the connection between estrogen supplementation and breast cancer. One theory is that estrogen may promote the division and multiplication of cells in your breasts, which increases the chance of mutations that can spur cancerous tumors to grow. Another theory suggests that estrogen may promote the growth of a person’s existing tumors.

However, there is still no solid evidence that estrogen HRT causes cancer.

Progestin and Breast Cancer

Progestin is a synthetic form of progesterone, a naturally occurring hormone. When you reach menopause, your body slows in its production of progesterone. Progestin is used in a type of HRT called estrogen progesterone/progestin hormone therapy (EPT). Like other HRTs, it treats menopausal symptoms.

The Women’s Health Initiative trial and other studies have found an increased risk of breast cancer in people who use EPT. The risk of breast cancer may increase the longer you use EPT, and there may be an increased risk you will have an abnormal mammogram within your first year of using an EPT.

Researchers have aimed to examine the role that EPT can play in your development of breast cancer. Studies have addressed different questions, like whether the form of progestin (pill or patch), how often it’s used, and how it’s been created can impact your risk of breast cancer.

Some scientists think that the way progestin influences the multiplication of cells in the breast may affect the development of breast cancer. Other researchers suggest that progestin created from testosterone as well as continuous use (versus cyclical use, which is only recommended for women who still have periods) are associated with increased chances of breast cancer.

Type of Breast Cancer

The use of HRT is associated with increased risk of specific types of breast cancer. A study published in Breast Cancer Research examined over 118,000 women between 50 and 71 years old. It found that combined HRT was associated with increased risk of:

  • Invasive breast cancer (cancer that extends beyond your breast)
  • In situ breast cancer (cancer contained to the ducts or lobes of your breast)
  • Additional breast cancers defined by the extent and location where the tumor started
  • Hormone-receptor-positive breast cancer (cancer cells containing estrogen and/or progesterone receptors)

Studies published in Nature Reviews of Clinical Oncology and The Lancet have found that the type of breast cancer associated with HRT was more likely to be estrogen-receptor positive. (In other words, the cancer cells of people who had undergone HRT contained estrogen receptors.) HRT-related breast cancer has also been associated with HER2 positive cancers, a type of breast cancer in which your cells make too many human epidermal growth factor receptor 2s (HER2).

Factors That Affect the Risk of Breast Cancer

Research since the WHI trial has highlighted several important findings about the patterns of characteristics of women with an increased risk of HRT-related breast cancer.

Estrogen-Only Versus Combined Estrogen-Progestin HRT

Collectively, research shows that your risk of breast cancer is greater when you take combined estrogen and progestin HRT, especially as compared to people who take estrogen-only HRT. According to still more studies, when looked at on its own, estrogen-only HRT is sometimes associated with a risk of breast cancer, and sometimes not.

Duration of Use

The risk of breast cancer has also been found to increase in people who engaged in long-term estrogen-progestin HRT. A study found that for every five years such HRT was used, there was a 10-percent increase in a person’s risk of breast cancer. Another study saw its participants’ risk of breast cancer go up with every year that a person used combined HRT.

Studies have also found that the risk of breast cancer decreases greatly after a postmenopausal woman stops taking combined HRT. Short-term use (five years or less) of combined HRT in the past may not be associated with breast cancer.

Body Mass Index and Breast Density

Factors like body mass index (BMI) and breast density have been found to be associated with HRT-related risk of breast cancer. Studies have found increased risk of breast cancer in women with leaner BMIs who take estrogen-only HRT.

The risk of HRT-related breast cancer has also been found to be higher in women who have more dense breasts. One study found the use of combined HRT may increase the density of breast tissue. Generally, more dense breasts are considered a risk factor for breast cancer and can make reading the results of a mammogram more difficult.

How To Manage Symptoms of Menopause Without HRT

There are other ways of managing postmenopausal symptoms that may have lower risks. You could try these approaches:

  • Limit caffeine and alcohol to keep cool and reduce hot flashes.
  • Practice relaxation techniques like breathing exercises, meditation, or acupuncture.
  • Maintain a healthy weight and exercise regularly.
  • Ask your doctor about medications that don’t contain hormones.
  • Talk to your doctor about “local” hormone therapies that haven’t been linked to increased risk of cancer (like creams to treat symptoms like vaginal dryness).

Your doctor may be your best partner in treating symptoms of menopause. Talk to them for their suggested alternatives. And remember lifestyle factors like dressing in removable layers, wearing breathable clothing, and keeping ice packs handy can also help keep you comfortable.

Is HRT Right for You?

If you have severe postmenopausal symptoms, your doctor will weigh the pros and cons of you using HRT. If you’ve had a diagnosis of breast cancer, have tested positive for a breast cancer gene (BRCA1 or BRCA2), or have other risk factors, your doctor will likely not prescribe HRT.

If you don’t have any risk factors, HRT may help if your menopausal symptoms are severe. And you may reap other potential benefits, like lowering your risk of osteoporosis.

If you do use postmenopausal hormone therapy, make sure that you and your doctor discuss the risks and benefits and other side effects. You may need to get regular mammograms to check for growths and abnormalities in your breast tissue.

Talk To Others Who Understand

Talking to other people who understand what you are going through can be a great source of emotional support. On MyBCTeam, the social network for people with breast cancer and their loved ones, more than 54,000 members come together to ask questions, give advice, and share their stories with others who understand life with breast cancer.

Are you trying to manage menopause with breast cancer? Share your experience in the comments below, or start a conversation by posting on your Activities page.

References
  1. Menopausal Hormone Therapy and Cancer — National Cancer Institute
  2. Hormone Therapy for Menopause Symptoms — Cleveland Clinic
  3. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women’s Health Initiative Randomized Controlled Trial — JAMA
  4. Menopausal Hormone Therapy and Breast Cancer Risk — Susan G. Komen
  5. Current Breast Cancer Risks of Hormone Replacement Therapy in Postmenopausal Women — Expert Opinion on Pharmacotherapy
  6. Menopausal Hormone Therapy — Susan G. Komen
  7. Use of Postmenopausal Hormone Therapies and Risk of Histology and Hormone Receptor-Defined Breast Cancer: Results From a 15-Year Prospective Analysis of NIH-AARP Cohort — Breast Cancer Research
  8. Hormone Replacement Therapy and the Risk of Breast Cancer — Nature Reviews: Clinical Oncology
  9. Type and Timing of Menopausal Hormone Therapy and Breast Cancer Risk: Individual Participant Meta-Analysis of the Worldwide Epidemiological Evidence — The Lancet
  10. Breast Cancer Subtypes — Breast Cancer Prevention Partners
  11. Effect of Hormones Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin — Journal of the National Cancer Institute
  12. Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk — JAMA
  13. Use of Hormone Replacement Therapy and Risk of Breast Cancer: Nested Case-Control Studies Using the QResearch and CPRD Databases — The British Medical Journal
  14. Hormone Replacement Therapy, Breast Cancer Risk Factors, and Breast Cancer Risk: A Nationwide Population-Based Cohort — Cancer Epidemiology, Biomarkers, and Prevention
  15. Estrogen-Plus-Progestin Use and Mammographic Density in Postmenopausal Women: Women's Health Initiative Randomized Trial — Journal of the National Cancer Institute
  16. Using HRT — Breastcancer.org
  17. Hormone Therapy: Is It Right for You? — Mayo Clinic
  18. Treating Menopausal Symptoms — Susan G. Komen
All updates must be accompanied by text or a picture.
Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Elizabeth Wartella, M.P.H. is an Associate Editor at MyHealthTeam. She holds a Master's in Public Health from Columbia University and is passionate about spreading accurate, evidence-based health information. Learn more about her here.

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