HRT Update Regarding Breast Cancer Risk Advised in EU

Roxanne Nelson, RN, BSN

May 18, 2020

In concluding their review of hormone replacement therapy (HRT) and the associated risk of breast cancer, the EU Pharmacovigilance Risk Assessment Committee (PRAC) has recommended updating current safety information.

PRAC is the European Medicine Agency's (EMA) committee that is responsible for assessing the safety of human medications, and it has based this latest update on evidence from a large individual participant meta-analysis that was published last year in The Lancet, and reported at the time by Medscape Medical News.   

The study confirmed that all types of menopausal HRT, with the exception of vaginally inserted estrogen, were associated with an increased risk of developing breast cancer. Even after HRT was stopped, some excess risk could persist for a decade, with the size of risk dependent on the duration of use.

Specifically, use of HRT for 10 years resulted in about twice the excess breast cancer risk associated with 5 years of use.

A previous meta-analysis published in 1997 had reported an association between HRT and breast cancer (The Lancet. 1997;350:1047-1059), and the subject received widespread attention when the increased risk for breast cancer with combination HRT was reported in 2002 from the Women's Health Initiative and in 2003 from the Million Women study. These highly publicized reports led to a dramatic fall in the use of HRT.

Since that time, other studies have suggested there is no increase, or little increase, in breast cancer risk. However, a 2016 study published in the British Journal of Cancer reported that risk for breast cancer was increased to a much greater extent than had previously been reported, and the longer the duration of use, the greater the risk.

New Recommendations

After evaluating all of the available evidence, the PRAC recommended the following changes be implemented in the product information:

  • For both combined estrogen-progestogen and estrogen-only HRT, the updated product information will reflect that the known higher risk of breast cancer becomes clear after about 3 years of using the products. The extra risk will decline over time after HRT is stopped, but the amount of time required to return to baseline depends largely on the duration of prior HRT use. The new information will indicate that this risk may persist for 10 years or more in women who have used HRT for more than 5 years.

  • The effect on breast cancer risk is currently unknown for conjugated estrogens/bazedoxifene (Duavive, Pfizer). But as these products do contain conjugated estrogens, the information will be updated to reflect the new information related to estrogen-only therapy.   

  • Updated product information on tibolone-containing HRT will reflect the fact that there are no data available for persistence of risk after treatment ends. However, a similar pattern cannot be ruled out.

  • For low-dose vaginally applied estrogen, the product information will be updated to reflect that current evidence does not show an increased breast cancer risk in women without a past history of the disease. It remains unknown if this mode of HRT can be safely used in women who had breast cancer in the past.

The PRAC emphasized that women should only use HRT to treat menopausal symptoms at the lowest dose and for the shortest possible time that works for them, and this information is already included in HRT product information. Additionally, women should also have regular checkups, including breast screening, that are in line with current recommendations and seek medical attention if they notice any changes in their breasts.

Meeting Highlights from the Pharmacovigilance Risk Assessment Committee (PRAC), May 11-14, 2020. Full text

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