National Breast Cancer Coalition

Call to Action Online - October 8, 2019

NBCC advocate perspective on recent research news and developments in breast cancer.

Current Facts About Menopausal Hormone Replacement Therapy and Breast Cancer

Many women who are post-menopausal take hormone replacement therapy (HRT), mostly to quell the debilitating side effects that occur in some women.  There are risks associated with HRT and many women have had questions about them.  One question is whether HRT increases a woman’s risk of breast cancer That question was finally answered in the early 2000s, with results from two studies, the Women’s Health Initiative (WHI)(1) and the Million Women Study (MWS).(2) These studies showed that HRT increases the risk of breast cancer, and that the effect is substantially greater for the use of estrogen-plus-progestin HRT combinations than for estrogen only formulations. WHI specifically estimated a 24% increase in the risk for breast cancer due to estrogen-plus-progestin formulations. The MWS likewise demonstrated an increase in breast cancer risk for combination HRTs, and that breast cancer risk goes up with increasing total duration of use of HRT.

Almost immediately after the 2002 WHI publication, HRT use among existing and new users in the United States dropped precipitously by approximately 28% and 50%, respectively, among postmenopausal women. This was followed by sharp and significant drop in the incidence of breast cancer of up to 22% between 2001-2002 and 2005-2006, in the US and European populations, consistent with the drop in HRT use. Declines in the rates of breast cancer were strongest for 50-60-year-old women (those most likely to be current users of HRT), affected mainly ER+ and PR+ breast cancers.(3) However, over the intervening years, debate over the interpretation of the WHI results and the risks associated with HRT use have persisted, and current clinical practice guidelines continue to recommend the use of HRT (i.e., for limited durations) in women suffering side effects associated with menopause or at risk of fractures.(4-6)

Two new publications released in the August 29, 2019 issue of the Lancet(7,8) add to the evidence regarding HRT and breast cancer risk. The first study is an individual patient-level meta-analysis conducted by the Collaborative Group on Hormonal Factors in Breast Cancer(7) derived from 58 studies, including 24 prospective cohort studies. The primary aim of this analysis was to synthesize all available data to date, to examine the long-term effects of HRT. This analysis takes into consideration, type of therapy used (i.e., estrogen only or combination therapy), age at start of HRT, duration of use, and length of time since previous use.  The second published study was a 20-year follow-up of the MWS, which was included in the above described meta-analysis. In addition to the above considerations, this analysis also reported on risk of breast cancer mortality associated with HRT use.(8) The key take-away from these studies—HRT increases risk of developing invasive breast cancer and of dying of breast cancer. This risk is highest for individuals who use combination estrogen-progestin based therapies, and increases with the length of duration of use.

In terms of the calculated absolute risk of developing breast cancer, assuming 5 years of HRT, starting at the age of 50 years would increase the incidence of breast cancer by:

  • 1 in every 50 users of estrogen plus daily progestin therapy;

  • 1 in every 70 users of estrogen plus intermittent progestin therapy; and

  • 1 in every 200 users of estrogen-only therapies.

The increased risk of breast cancer incidence would be double the above numbers for individuals taking HRT for 10 years.

The mortality assessment presented in the 20-year follow-up of the MWS reported that among women who had previously used HRT for less than 5 years (mean: about 1 year), there was no significant excess mortality from breast cancer (rate ratio 0·99, 95% CI 0·91–1·06). By contrast, past users with longer prior use of HRT (mean: about 8 years) did have higher mortality from breast cancer over the next 20 years (1·24, 1·12–1·38, p=0·0005). The magnitude of mortality risk is highest for individuals using combination, estrogen-progestin formulations for greater than a five-year duration.

The current analyses reinforce previous findings regarding the breast cancer-associated risks from the use of estrogen-progestin combination therapies.

Interested in learning more about the science of breast cancer? Apply to the Project LEAD Institute, NBCC’s premier science training program, and attend the annual Advocate Leadership Summit to learn directly from the country’s preeminent breast cancer researchers.

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  1. Rossouw JE, Anderson GL, Prentice RL, et al. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33. PubMed PMID: 12117397.

  2. Beral V; Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003 Aug 9;362(9382):419-27. Erratum in: Lancet. 2003 Oct 4;362(9390):1160. PubMed PMID: 12927427.

  3. Verkooijen HM, Bouchardy C, Vinh-Hung V, et al. The incidence of breast cancer and changes in the use of hormone replacement therapy: a review of the evidence. Maturitas. 2009 Oct 20;64(2):80-5. Epub 2009 Aug 25. Review. PubMed PMID: 19709827.

  4. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017 Jul;24(7):728-753. 1. PubMed PMID: 28650869.

  5. Goodman NF, Cobin RH, Ginzburg SB, Katz IA, Woode DE; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of menopause: executive summary of recommendations. Endocr Pract. 2011 Nov-Dec;17(6):949-54. PubMed PMID: 22193145.

  6. National Institute of Clinical Excellence. Menopause: diagnosis and management, Accessed 27th September 2019

  7. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019 Aug 29. PubMed PMID: 31474332.

  8. Beral V, Peto R, Pirie K, Reeves G. Menopausal hormone therapy and 20-year breast cancer mortality. Lancet. 2019 Aug 29. PubMed PMID: 31474331.