Hormone replacement therapy and breast cancer: heterogeneous risks by race, weight, and breast density

Although studies have demonstrated a positive association between hormone replacement therapy (HRT) and breast cancer risk, this association may vary by patient factors.

We analyzed 1642824 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.

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).

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.