Mixed Results for Hormone Replacement Therapy and Breast Cancer Risk

by Karuna Jaggar, Executive Director

A large, federally-funded study evaluating the use of hormone replacement therapy (HRT) to reduce the risk of heart disease, bone loss, and other effects of menopause was stopped early in 2002 when researchers found more breast cancers among those using HRT. New follow-up analysis of the study, called the Women’s Health Initiative (WHI) and presented at SABCS in 2019, reinforced those earlier findings but also unexpectedly found that a subset of women, those using HRT without progesterone, had a lower risk of being diagnosed with breast cancer, dying from breast cancer, and death from any cause. 

It’s important to note that hormone therapy commonly used to treat hormone positive breast cancer, the most common subtype, is not the same as hormone replacement therapy used for people going through menopause. Because estrogen alone can cause uterine cancer, HRT is usually given with progesterone to “oppose” the estrogen and protect the uterus.

Between 1993 and 1998, the WHI enrolled postmenopausal women with no history of breast cancer. Participants were randomized to receive HRT or placebo. More than 16,000 women received estrogen and progesterone or placebo. Another 10,000+ women who had undergone a hysterectomy received estrogen only or placebo.

This analysis included a very large population of women, ranging in age 50-79 and with no prior breast cancer. They were followed for more than 19 years. The researchers looked at both estrogen-only and estrogen plus progesterone HRT to evaluate the effect on breast cancer risk—with surprising results.

For women who have never had breast cancer, based on 19 years follow-up in the randomized trials of the Women’s Health Initiative, estrogen-only HRT reduced the incidence of breast cancer as well as deaths from any cause, including breast cancer—which has never been previously published. In contrast, long-term results from the WHI presented at SABCS showed that women who use estrogen and progesterone after menopause have a small but statistically significant increased risk of breast cancer more than a decade after they stop taking the pills. Because estrogen-only HRT can’t be given to women who have not had their uterus removed, it’s important to caution that this data does not mean that women should have hysterectomies so they can go on estrogen-only HRT!

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