While expression of ER is a defining feature of breast cancers with the most differentiated luminal phenotype, our data supports a functional role for AR signaling in the promotion of luminal differentiation in breast cancers regardless of ER status, which could mechanistically explain the positive association between AR expression and tumor indolence, luminal phenotypic features as well as prolonged disease-free survival in multiple subtypes of this disease [8, 46–49]. This evidence concerns the gene ESR1 and breast cancer.