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Underlying Breast Cancer Risk and Menopausal Hormone Therapy

Richard J Santen 1, Daniel F Heitjan 2, Anne Gompel 3, Mary Ann Lumsden 4, JoAnn V Pinkerton 1, Susan R Davis 5, Cynthia A Stuenkel 6

DOI: 10.1210/clinem/dgaa073

The recent Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) publication calculated the attributable risk of breast cancer from use of estrogen alone and estrogen plus a synthetic progestogen for <5 to ≥15 years of use. This CGHFB report calculated attributable risk based on their findings of relative risk from pooled data from 58 studies. Notably, neither the CGHFBC nor other previous studies have examined the effect of underlying risk of breast cancer on attributable risk. This omission prompted us to determine the magnitude of the effect of underlying risk on attributable risk in this Perspective. Meaningful communication of the potential risk of menopausal hormonal therapy requires providing women with the estimated risk above their existing underlying risk (i.e. attributable risk). Therefore we have estimated attributable risks from the data published by the CGHFBC, taking into account varying degrees of underlying risk. Based on the Endocrine Society Guideline on Menopausal Hormone Therapy (MHT), we divided groups into three categories of risk: low (1.5%), intermediate (3.0%), and high (6.0%) underlying risk of breast cancer over 5 years. In women taking estrogen plus a synthetic progestogen (E+SP) for 5-9 years, the attributable risks of MHT increased from 12, to 42, to 85 additional women per 1000 in the low, intermediate, and high risk groups respectively. The attributable risks for estrogen alone were lower but also increased based on underlying risk. Notably, the attributable risks were amplified with duration of MHT use which increased both relative risk and breast cancer incidence.