Steroid hormone receptors (HRs) are ligand-activated transcription factors that play a pivotal role in breast development and carcinogenesis. It is well established that estrogen receptor (ER) signaling is a major proliferative driver in estrogen receptor-positive breast cancers (ER+ BC) and it is routinely targeted pharmacologically. However, endocrine resistance is a frequent clinical problem and alternative therapeutic strategies are needed. Interestingly, 90% of ER+ BC co-express the androgen receptor (AR), but its precise role in BC is not yet fully understood. Increased plasma testosterone levels and exposures to androgenic progestins have been linked to increased risk for HR+ BC, suggesting AR signaling might be involved in pro-tumorigenic processes. Nevertheless, recent preclinical studies report both tumor suppressing and tumor promoting effects of AR signaling in ER+ BC. This multifaceted scenario points to a complex and context-dependent role of AR in breast cancer onset and progression. The study of ER+ BC has been hindered by the lack of preclinical models that can faithfully recapitulate the human disease. To overcome this limitation, our lab has recently adopted the mouse intraductal (MIND) model and demonstrated that patient-derived ER+ BC as well as normal breast epithelial cells (NBECs) can be successfully established in vivo and retain hormone responses. In my doctoral research, we leveraged the MIND model to elucidate the role of AR in both normal and malignant breast cells in clinically relevant in vivo settings. Our findings reveal that ER+ BC patient-derived xenografts (PDXs) have decreased cell proliferation when stimulated with the pure AR agonist dihydrotestosterone (DHT) in the presence of estradiol (E2), whereas no effect is induced in estrogen-deprived conditions. Mechanistically, AR action on the chromatin leads to transcriptional repression of ER targets and cell cycle genes, as well as the blockage of ER expression. Conversely, we find that NBECs grown under postmenopausal E2 level respond to DHT with upregulation of mitotic pathways and increased cell proliferation. However, the proliferative effect elicited by AR stimulation in NBECs can be reversed upon estrogen supplementation, suggesting that ER signaling acts as the molecular switch that dictates the divergent response to androgens between the normal and malignant breast cells. In summary, this study provides a comprehensive understanding of AR signaling in both normal and malignant breast cells within physiological in vivo environments, shedding light on crucial context-dependent effects.