Aim: We report the association between menopausal hormone therapy (MHT) types and incident breast cancer (invasive/DCIS) in ~20,000 Australian women, after adjusting for breast density and other associated factors.
Methods: Our dataset comprised baseline questionnaires, breast density, screening and cancer registry data for Lifepool cohort participants (mostly from BreastScreen) aged 40-75 without a personal history of breast cancer. We categorised self-reported current MHT formulations as: EPT (oestrogen and progestogen combinations); ET (oestrogen-only); T (tibolone) or PT/LET (progestogen/progesterone only preparations/other estrogen-only creams and pessaries). The primary outcome was incident breast cancer. We fitted multivariate Cox regression models adjusted for baseline breast density, age, age at first period, parity, breastfeeding, body mass index, region of birth, smoking status and strong family history. We excluded records with inadequate MHT information and applied multiple imputation for missing covariate data. Missing data ranged from 1.1% to 5.8% across covariates.
Results: 19,545 participants were included in the analysis, with baseline questionnaires completed between 06/03/2010 and 12/04/2015. There was total 518 (2.7%) incident breast cancers, with a mean follow-up of 7.1 years (range: 61 days to 9.6 years). 19.7% of the study group were current users of MHT at baseline (4.1% EPT, 11.2% ET, 3.4% T and 1.0% SPT/LET). In the fully adjusted model, compared to never users of MHT, current users had a significantly higher risk of developing breast cancer (HR=1.4 (95%CI 1.2-1.8), p<0.001). This held for most types assessed: EPT HR=1.7 (95%CI 1.2-2.5), p=0.01; ET HR=1.4 (95%CI 1.1-1.7), p=0.02; and T HR=1.7 (95%CI 1.2-2.5), p=0.01.
Conclusions: Various types of MHT significantly increase breast cancer risk after accounting for breast density and other factors. This included combined oestrogen and progestogen, oestrogen-only and tibolone. MHT use continues to be an important risk factor for breast cancer and should be considered in recommendations for breast cancer prevention.