Breast Cancer and Menopausal Hormone Therapy: What Do the New Data Mean?

Andrew M. Kaunitz, MD


November 13, 2020

This transcript has been edited for clarity.

More than 15 years ago, the Women's Health Initiative (WHI) randomized trials[1,2] reported that estrogen-progestin therapy (EPT) modestly increased the risk for invasive breast cancer while estrogen therapy (ET) reduced risk. The findings of a new British study are similar to those of the WHI.

In a recent issue of The BMJ, investigators used British primary care databases to identify almost 100,000 women with breast cancer as well as over 450,000 control women.

The investigators adjusted their analyses for parameters including mammography, body mass index (BMI), and ethnicity.

Ever-use of EPT was associated with an odds ratio for breast cancer of 1.26 whereas ET had an odds ratio for breast cancer of 1.06.

Among women aged 50-59 who used EPT for 5 or more years, 15 additional breast cancers were diagnosed per 10,000 person-years; for ET users, the attributable risk was 3 per 10,000.

Although risks increased with longer duration of hormone therapy, this trend was less clear with ET than with EPT. In addition, the increased risks were less pronounced in obese women.

With respect to progestogens used in EPT users, risks were similar with medroxyprogesterone acetate, norethindrone acetate, and levonorgestrel.

Likewise, risk did not vary with respect to estrogen dose or with oral vs transdermal route of administration. In contrast with systemic hormone therapy, vaginal estrogen was not associated with any change in risk for breast cancer.

Among users of EPT, the excess risks in both this UK study and the US WHI trial were essentially identical. The authors point out that the mean BMI of the UK study participants was higher than in the WHI, and they speculated that this difference might explain the differing findings with respect to ET use.

Considering both WHI findings and those of this high-quality UK observational study, we should counsel our patients that while EPT increases risk for breast cancer, the magnitude of this excess risk is small and should be weighed against hormone therapy benefits, including treatment of bothersome menopausal symptoms and prevention of osteoporosis. As for ET, if an elevated risk for breast cancer is present, this excess risk is minimal.

Thank you for the honor of your time. I am Andrew Kaunitz.

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