2X MATCH: 2X MATCH Today, your gift is DOUBLED for 2X the impact on lifesaving research.
Clear Search

What Research Says About HRT and Breast Cancer Risk

By BCRF | November 12, 2024

For some women, hormone replacement therapy (HRT) can alleviate symptoms without increasing risk

Many women face tough decisions about managing their menopausal symptoms. Hormone replacement therapy (HRT) is often a point of concern and confusion, but the prevailing guidance on its use has evolved, thanks to ongoing research. For some women, HRT may offer relief from symptoms like hot flashes, sleep disturbances, and mood swings—without increasing breast cancer risk.

Below, BCRF dives into how research has improved our understanding of HRT and breast cancer risk, including what people with a history of breast cancer need to know.

A brief history of HRT

In the early 1940s, the FDA first allowed companies to market hormone medications to alleviate menopausal symptoms. By the 1960s, women were widely prescribed HRT.

But, in 2002 this changed when part of the Women’s Health Initiative, a long-term national health study, was halted after data indicated that HRT increased risks of cardiovascular disease, stroke, pulmonary embolism, and breast cancer in women over 60. In the years that followed, women and their doctors largely abandoned the treatment.

Today, new findings and updated research on HRT and breast cancer risk are providing women with more knowledge and empowering them to make better, more informed decisions about their health with their doctors.

What is HRT?

Hormone replacement therapy, or postmenopausal hormone therapy, is a treatment that replaces hormones no longer made by the ovaries as a woman enters menopause. One of HRT’s major benefits is that it protects against osteoporosis, a condition that develops when bone density and mass decrease due to a decrease in ovarian estrogen production.

There are two main types of HRT. A low-dose estrogen-only therapy is used only when a woman has already had surgery to remove her uterus (hysterectomy). While this treatment can increase a woman’s risk of endometrial cancer, it has fewer long-term risks compared to combination therapy, the other main type. Combination therapy includes both estrogen and progesterone (also called progestin). It can be used by those with a uterus since progestins help reduce the risk of endometrial cancer.

HRT can be used systemically in pill form, or topically in the form of a skin patch, gel, cream or spray. A topical vaginal cream is also available specifically to treat vaginal dryness and is not readily absorbed into the bloodstream. Systemic HRT addresses many of the symptoms associated with menopause, whereas topical HRT only relieves vaginal symptoms such as dryness and pain during sex.

Does HRT increase your risk of breast cancer?

Thanks to additional research, we now know that there are important factors to consider when assessing an individual’s personal risk of breast cancer when she has used HRT. The type and dose of HRT, how long it is used, the individual’s age at which therapy begins, and breast cancer history should all be carefully considered to determine the risks and benefits of HRT for women suffering from symptoms of menopause.

For example, a more-nuanced explanation is now available that further clarifies the relationship between HRT and breast cancer risk, as conclusions drawn from study data in 2002 were based largely on women older than 60. Findings from the 20-year follow-up to the WHI study published this year found that breast cancer risk increased with longer use of combination HRT, but absolute risk (the chance something will happen) was low compared to placebo, and women aged 50 to 59 had lower risk than women aged 60 and older. Estrogen-only HRT lowered breast cancer risk in women with prior hysterectomies in all age groups studied.

These findings are supported by another large study of women between the ages of 50 and 79 from the United Kingdom. In that study, researchers found higher risks associated with longer use of systemic combination HRT. However, short-term (less than five years) past use of combination HRT was not associated with an increased risk.

Depending on the individual, the benefits of HRT—relief from menopause symptoms and bone health protection—may outweigh the small but real risks. Increasingly, researchers are finding that younger menopausal women with no history of breast cancer may experience significant improvements in quality of life by relieving their menopause-related symptoms through HRT. 

What do women with a history of breast cancer need to know about HRT?

Systemic HRT of any kind is not currently recommended for women who have a history of breast cancer. A 2021 review of systemic HRT in women with a history of breast cancer found that HRT significantly increased the risk of breast cancer recurrence, especially in patients with hormone receptor (HR)–positive disease, the most commonly diagnosed subtype of breast cancer. Another smaller clinical trial testing the safety of HRT after breast cancer was ended because results indicated an unacceptable risk for women exposed to HRT with a history of breast cancer.

While lifesaving, some chemotherapies and hormone therapies used to treat breast cancer can induce a temporary or permanent menopause. Radiation and surgical removal of the ovaries can also cause women to experience menopause symptoms. In these cases, systemic HRT to treat symptoms of menopause may not be an option due to an increased risk of recurrence.

Certainly, more research is needed to further understand the biological drivers of menopausal symptoms and how to improve them without using HRT in women with a history of breast cancer.

What can take the place of HRT after breast cancer?

Talk to your doctor about your options regardless of whether you have had breast cancer.

Improving general health by quitting smoking, cutting back on alcohol and caffeine, and decreasing body weight can improve menopausal symptoms. Eating smaller meals and avoiding spicy foods may also alleviate some symptoms. Foods and supplements containing estrogen-like compounds, called phytoestrogens, found in soy, legumes, and fruits and vegetables may also help, but more research is needed to confirm these benefits.

A limited number of studies have shown that cognitive behavioral therapy, acupuncture, and yoga may help improve a subset of the symptoms associated with menopause. In addition, topical HRT and vaginal moisturizers may be an option for women with a history of breast cancer who are experiencing some vaginal symptoms associated with menopause. That was backed up by a large meta-analysis, published in November 2024, of eight observational studies that revealed use of vaginal estrogen in patients with a history of breast cancer was not associated with an increased risk of recurrence, breast cancer-specific mortality, or overall mortality.

Non-hormonal medications and complementary therapies can also be prescribed to address symptoms. Research conducted by BCRF investigator Debra Barton has shown vitamin E to be effective against hot flashes. Other drugs can be prescribed to address menopause symptoms including:

  • Fezolinetant (Veozah®), a drug recently approved to treat hot flashes
  • Clonidine (Catapres®), a drug that lowers blood pressure and heart rate
  • Oxybutynin (Ditropan®), a drug used to treat an overactive bladder
  • Gabapentin (Neurontin®), a drug that relieves nerve pain, has been shown to help reduce hot flashes
  • Some antidepressant drugs prescribed at a low dose

Of note, some antidepressants can interact with the hormone therapy drug tamoxifen used to treat and prevent breast cancer recurrence. A healthcare provider can provide additional information on specific drug interactions and should be consulted about alternative options for relieving menopausal symptoms.

How is hormone therapy for treating breast cancer different from HRT?

Hormone therapy for breast cancer should not be confused with HRT. These two types of therapy produce opposite effects. Hormone therapy for treating breast cancer, also called endocrine therapy, uses a set of drugs to lower hormone levels or block the action of the hormone at the receptor, thereby reducing a woman’s risk of breast cancer recurrence.

On the other hand, HRT is given to replace estrogen and progesterone and relieve menopausal symptoms. It can stimulate the growth of HR-positive breast cancer. Therefore, they are not equivalent, and the terms should not be used interchangeably. 

Ongoing research promotes progress

BCRF-supported research is investigating the impact of hormones on breast cancer risk. Dr. Joyce Slingerland is interested in how obesity and post-menopausal estrogen increase risk and promote estrogen receptor (ER–positive breast cancer progression. She has found that estrone, the main type of estrogen produced after menopause and observed at levels up to three times higher in women with obesity, contributes to inflammation in the breast and drives metastatic spread.

Dr. Carol Fabian is testing a combination of bazedoxifene and conjugated estrogen (Duavee®) as a safe alternative to endocrine therapy that does not initiate or worsen menopause symptoms in women with a high risk of breast cancer. She has found that the treatment is associated with improvements in menopause-related symptoms, as reported by trial participants, and a reduction in breast density and factors in the blood known to promote breast cancer growth.

As researchers gather more data and expand our understanding, they continue to shed light on the complex, dynamic relationships between hormones, menopause, and cancer risk. This deeper insight may offer clearer guidance for women, whether they have a history of breast cancer or not.

References

Barton, D. L., Loprinzi, C. L., Quella, S. K., Sloan, J. A., Veeder, M. H., Egner, J. R., Fidler, P., Stella, P. J., Swan, D. K., Vaught, N. L., & Novotny, P. (1998). Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. Journal of Clinical Oncology, 16(2), 495–500. https://doi.org/10.1200/jco.1998.16.2.495

Carter, D. (2019, October 8). Does breast cancer treatment cause menopause? MD Anderson Cancer Center. https://www.mdanderson.org/cancerwise/7-things-to-know-about-menopause-and-breast-cancer.h00-159306990.html

De Blok, C. J. M., Wiepjes, C. M., Nota, N. M., Van Engelen, K., Adank, M. A., Dreijerink, K. M. A., Barbé, E., Konings, I. R. H. M., & Heijer, M. D. (2019). Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands. BMJ, l1652. https://doi.org/10.1136/bmj.l1652

Holmberg, L., & Anderson, H. (2004). HABITS (hormonal replacement therapy after breast cancer—is it safe?), a randomised comparison: trial stopped. The Lancet, 363(9407), 453–455. https://doi.org/10.1016/s0140-6736(04)15493-7

Manson, J. a. E., Chlebowski, R. T., Stefanick, M. L., Aragaki, A. K., Rossouw, J. E., Prentice, R. L., Anderson, G., Howard, B. V., Thomson, C. A., LaCroix, A. Z., Wactawski-Wende, J., Jackson, R. D., Limacher, M., Margolis, K. L., Wassertheil-Smoller, S., Beresford, S. A., Cauley, J. A., Eaton, C. B., Gass, M., . . . Wallace, R. B. (2013). Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA, 310(13), 1353. https://doi.org/10.1001/jama.2013.278040

Manson, J. E., Crandall, C. J., Rossouw, J. E., Chlebowski, R. T., Anderson, G. L., Stefanick, M. L., Aragaki, A. K., Cauley, J. A., Wells, G. L., LaCroix, A. Z., Thomson, C. A., Neuhouser, M. L., Van Horn, L., Kooperberg, C., Howard, B. V., Tinker, L. F., Wactawski-Wende, J., Shumaker, S. A., & Prentice, R. L. (2024). The Women’s Health Initiative randomized trials and clinical practice. JAMA. https://doi.org/10.1001/jama.2024.6542

Menopausal hormone therapy and cancer risk. (n.d.). American Cancer Society. https://www.cancer.org/cancer/risk-prevention/medical-treatments/menopausal-hormone-replacement-therapy-and-cancer-risk.html

Menopause – Symptoms and causes. (n.d.). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/menopause/symptoms-causes/syc-20353397

Poggio, F., Del Mastro, L., Bruzzone, M., Ceppi, M., Razeti, M. G., Fregatti, P., Ruelle, T., Pronzato, P., Massarotti, C., Franzoi, M. A., Lambertini, M., & Tagliamento, M. (2021). Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis. Breast Cancer Research and Treatment, 191(2), 269–275. https://doi.org/10.1007/s10549-021-06436-9

Professional, C. C. M. (2024, August 5). Hormone therapy for menopause symptoms. Cleveland Clinic. https://my.clevelandclinic.org/health/treatments/15245-hormone-therapy-for-menopause-symptoms

Qureshi, R., Picon-Ruiz, M., Sho, M., Van Booven, D., De Paiva, V. N., Diaz-Ruano, A. B., Ince, T. A., & Slingerland, J. (2022). Estrone, the major postmenopausal estrogen, binds ERa to induce SNAI2, epithelial-to-mesenchymal transition, and ER+ breast cancer metastasis. Cell Reports, 41(7), 111672. https://doi.org/10.1016/j.celrep.2022.111672

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. (2019). The Lancet, 394(10204), 1159–1168. https://doi.org/10.1016/s0140-6736(19)31709-x

UCSF Health. (2024, May 21). Menopause and breast cancer. ucsfhealth.org. https://www.ucsfhealth.org/education/menopause-and-breast-cancer

Vinogradova, Y., Coupland, C., & Hippisley-Cox, J. (2020). Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ, m3873. https://doi.org/10.1136/bmj.m3873