Association between menopausal hormone therapy, mammographic density and breast cancer risk: results from the E3N cohort study

Abstract

Background Menopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study. Methods We used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association between MHT and mammographic density was evaluated by linear regression models. We applied mediation modelling techniques to estimate, under the hypothesis of a causal model, the proportion of the effect of MHT on BC risk mediated by percent mammographic density (PMD) for BC overall and by hormone receptor status. Results Among MHT users, 4.2% used exclusively oestrogen alone compared with 68.3% who used exclusively oestrogens plus progestogens. Mammographic density was higher in current users (for a 60-year-old woman, mean PMD 33%; 95% CI 31 to 35%) than in past (29%; 27 to 31%) and never users (24%; 22 to 26%). No statistically significant association was observed between duration of MHT and mammographic density. In past MHT users, mammographic density was negatively associated with time since last use; values similar to those of never users were observed in women who had stopped MHT at least 8 years earlier. The odds ratio of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by PMD was 34% for any BC and became 48% when the correlation between BMI and PMD was accounted for. These effects were limited to hormone receptor-positive BC. Conclusions Our results suggest that, under a causal model, nearly half of the effect of MHT on hormone receptor-positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.

A pragmatic approach to the management of menopause

“…Approaches to managing mastalgia include minimizing estrogen to the lowest effective dose or using conjugated estrogens, cyclic progestin dosing, tibolone or the TSEC (when available). 49 …”

“…Approaches to managing mastalgia include minimizing estrogen to the lowest effective dose or using conjugated estrogens, cyclic progestin dosing, tibolone or the TSEC (when available). 49 Migraine is not a contraindication to the use of systemic menopausal hormone therapy. Migraine symptoms can be improved for some patients by using regular, continuous dosing of both estrogen and progesterone.…”

The 100 top-cited articles in menopausal syndrome: a bibliometric analysis

“…Nearly half of the effect of MHT on the risk of hormone receptor-positive BC is mediated by breast density. Indicate that we should use MHT with caution for women [ 56 , 57 ]. cCNE2 may be a candidate gene for estrogen-progestin-induced breast cancer.…”

Association Between Lifestyle Changes, Mammographic Breast Density, and Breast Cancer

“…Fornili et al 64 described an association between MHT, MBD, and BC risk limited to hormone receptor–positive BCs only. No association was found between MHT and hormone receptor–negative BCs.…”