Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway

Abstract

Background: It is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs.

Methods: We estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference.

Results: We included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31-2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35-1.96) to Kliogest®: 2.67 (2.37-3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86-2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83-2.30) than screen-detected (HR 1.33, 95% CI 1.26-1.41) BC in women 50-71 years. HRs for HT use decreased with increasing BMI.

Conclusions: The use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.

Fig. 1. Use of menopausal hormone therapy and risk of breast cancer according to the duration of use in current users compared to non-users in a 1:10 nested case–control sample.

Hazard ratios (HRs) and 95% confidence intervals (CIs) from stratified Cox regression with age as time scale (age-adjusted) and additionally adjusted for ethnicity, number of children, education, income, health region, screening attendance (never, <2.5 years since last screening, ≥2.5 years since last screening), use of antidiabetics (A10), antithrombotic agents (B01), antihypertensives (C02), diuretics (C03), beta-blockers (C07), calcium channel blockers (C08), angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (C09), lipid-modifying agents (C10), uterotonics and other gynecologicals (G02), urologicals (G04), thyroid therapy (H03) and treatment of bone diseases (M05). Estimates for mixed use not shown. ET oestrogen, NETA norethisterone acetate.