Hormone Replacement Therapy and Breast Cancer: Heterogeneous Risks by Race, Weight, and Breast Density

Background Although studies have demonstrated a positive association between hormone replacement therapy (HRT) and breast cancer risk, this association may vary by patient factors. Methods We analyzed 1 642 824 screening mammograms with 9300 breast cancer cases in postmenopausal women aged 45 years or older derived from the Breast Cancer Surveillance Consortium, a longitudinal registry of mammography screening in the United States. Multiple imputation methods were used to accommodate missing data for HRT use (14%) and other covariables. We performed logistic regression to estimate odds ratios (ORs) for breast cancer associated with HRT use within strata of race/ethnicity, age, body mass index (BMI), and breast density, with two-way interaction terms between HRT use and each key covariable of interest. P values for assessing possible interactions were computed from Wald z statistics. All statistical tests were two-sided. Results HRT use was associated with greater than 20% increased risk in white (OR = 1.21; 95% CI = 1.14 to 1.28), Asian (OR = 1.58; 95% CI = 1.18 to 2.11), and Hispanic women (OR = 1.35; 95% CI = 1.09 to 1.67) but not black women (OR = 0.91; 95% CI = 0.72 to 1.14; P-interaction = .04). In women with low/normal BMI and extremely dense breasts, HRT use was associated with the highest breast cancer risk (OR = 1.49; 95% CI = 1.21 to 1.83), compared with nonusers. In overweight/obese women with less-dense breasts, no excess risk was associated with HRT use (adjusted ORs = 0.96 to 1.03). Conclusions The impact of HRT use on breast cancer risk varies according to race/ethnicity, BMI, and breast density. This risk stratification could help in advising HRT use for the relief of menopausal symptoms.