My laboratory studies how reproductive hormones control normal breast development and how they contribute to breast carcinogenesis. When most studies on steroid hormone receptor signaling have been performed in simple in vitro systems such as breast cancer cell lines, my group seeks to unravel hormone action in physiologically and clinically relevant settings. A major hurdle to our understanding of hormone sensitive breast cancer has been the lack of physiologically and clinically relevant models to study the disease. My laboratory overcame this problem by grafting estrogen receptor positive (ER+) breast cancer cell lines and patient derived tumor cells into the milk ducts of immunocompromised mice. We demonstrated that when the ER+ tumor cells are provided with the adequate microenvironment they faithfully recapitulate the human disease including metastatic seeding. We can now reproducibly engraft normal breast epithelial cells and hormone-sensitive breast cancer cells from patients and experimentally manipulate and study them in vivo. This is complemented by recently developed mass spectrometry-based methods to measure multiple steroids in plasma allowing us to readily monitor hormone levels in experimental animals.