Menopausal hormone therapy and the risk of breast cancer by histological type and race: a meta-analysis of randomized controlled trials and cohort studies

Purpose: This meta-analysis investigated the association between the risk of breast cancer and hormone replacement therapy (HRT). Various stratified analyses were performed according to race (Asian/Westerner), HRT type [all hormone therapies, estrogen-only therapy (ET), or combined estrogen–progestin therapy (EPT)], histological breast cancer type (ductal/lobular/mixed ductal–lobular), and estrogen receptor status (ER-positive/ER-negative). Methods: A literature search was performed using Pubmed, Embase, and KoreaMed. Twenty-five epidemiological studies including 23 cohort studies and two randomized controlled trials were included in this meta-analysis. Results: Using a random-effects model, HRT use was found to be positively associated with the risk of breast cancer with a pooled hazard ratio (HR) of 1.33 [95% confidence interval (CI) 1.24, 1.44]. Compared with ET, EPT was more strongly associated with breast cancer risk. EPT was associated with both ductal and lobular breast cancer risks [for ductal breast cancer, HR = 1.51 (95% CI 1.28, 1.78); for lobular breast cancer, HR = 1.38 (95% CI 1.20, 1.60)]. According to ER status, all HRTs were associated with the risk of ER-positive breast cancer, but not with that of ER-negative breast cancer. Conclusions: Asian HRT users had a higher risk of breast cancer than western HRT users. Both ET and EPT were significantly associated with the risk of all breast cancer histological types and ER-positive breast cancer.