Androgen receptor expression in normal breast tissue and subsequent breast cancer risk

Sex steroid hormone signaling is critical in the development of breast cancers, although the role of the androgen receptor remains unclear. This study evaluated androgen receptor (AR) expression in normal breast tissue as a potential marker of breast cancer risk. We conducted a nested case–control study of women with benign breast disease (BBD) within the Nurses’ Health Studies. Epithelial AR expression was assessed by immunohistochemistry in normal tissue from the BBD biopsy and the percent of positive nuclei was estimated in ordinal categories of 10% for 78 breast cancer cases and 276 controls. Logistic regression models adjusting for the matching factors and BBD lesion type were used to calculate odds ratios (ORs) for the association between AR expression (tertiles: ≤10%, 11–30%, and >30%) and breast cancer risk. AR expression in normal breast tissue was not associated with subsequent breast cancer risk (OR(T3vsT1) = 0.9, 95% CI = 0.4–1.8, p trend = 0.68). In comparison with low AR/low ER women, ORs of 0.4 (95% CI = 0.1–1.2) for high AR/high ER women, 1.8 (95% CI = 0.4–7.8) for low AR/high ER women, and 0.7 (95% CI = 0.3–1.6) for high AR/low ER women were observed (p interaction = 0.21). Ki67 did not modify the association between AR expression and breast cancer risk (p interaction = 0.75). There was little evidence for an overall association between AR expression in normal breast tissue and breast cancer risk. These findings did not show that the AR association varied by Ki67 expression in normal breast tissue, though there was suggestive heterogeneity by ER expression.