Patient-Oriented Evidence That Matters

Twenty-Year Follow-Up of the Women's Health Initiative Trials: Lower Breast Cancer Mortality with Estrogen Alone, No Difference with Estrogen Plus Progesterone


Am Fam Physician. 2021 Jan 15;103(2):online.

Clinical Question

Does hormone therapy increase the risk of breast cancer incidence and mortality in postmenopausal women?

Bottom Line

The cumulative 20-year follow-up report from the Women's Health Initiative hormone therapy trials found significantly lower breast cancer incidence and mortality among postmenopausal women who previously took conjugated equine estrogen (CEE; Premarin) alone (with a prior hysterectomy) than in women who took a placebo. Women in the same age group who took estrogen plus progesterone have a significantly increased incidence of breast cancer compared with those who took a placebo, but no significant difference in breast cancer mortality. (Level of Evidence = 1b)


The report is a 20-year median cumulative follow-up of the Women's Health Initiative hormone therapy trials that evaluated the outcomes from giving CEE plus progesterone to postmenopausal women, 50 to 79 years of age, with an intact uterus, and giving CEE alone to women in the same age group with a previous hysterectomy. The original trials were stopped after 7.2 years because of an increased risk of stroke in the treatment groups. After the original trials were stopped, less than 4% of the women reported continuing hormone therapy. The previous cumulative 18-year follow-up report showed no significant differences in all-cause mortality, cardiovascular-related mortality, or cancer-related mortality in postmenopausal women who took CEE plus progesterone or CEE alone (with a prior hysterectomy) compared with women who took a placebo. This additional follow-up report focuses on breast cancer incidence and mortality. Using data obtained from regular surveillance of the National Death Index and cancer registries, as well as reports from next of kin, information was available for more than 98% of the 27,347 original participants. Compared with placebo, CEE alone was associated with a statistically significant lower breast cancer incidence (hazard ratio [HR] = 0.78; 95% CI, 0.65 to 0.93)

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see http://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

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This series is coordinated by Sumi Sexton, MD, editor-in-chief.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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