5-year breast cancer survival among African American women is 74%, significantly lower than the 88% survival observed in women of European white ancestry. Although this difference has, in the past, been largely attributed to socioeconomic factors, increasing data suggests that there are intrinsic differences in African American breast tissue compared with European whites. Risk factors for breast cancer have been extensively investigated, and a number of such factors involve breast differentiation, including timing of menarche and timing and number of pregnancies. Our laboratory has developed a novel tissue engineering system for human breast epithelial cells, both normal and malignant, that allows us to study breast differentiation and breast tumor biology in a dish. In this system, long-term cultures of normal primary epithelial cells first form 3-dimensional "epispheres," consisting of 40-100 cells, which can then differentiate into organotypic branching ducts and lobules. We have successfully established renewable cultures of normal breast epithelial cells from 48/48 non-diseased women undergoing breast reduction mammoplasty. Twelve of these women (25%) were African Americans socioeconomically matched with the European whites. This rate of success in establishing human breast-derived cultures, and their ability to form complex functional ductal structures, is unprecedented. A significant model for the timing of ductal formation in culture (P = 0.005) involved only donor ancestry and height. Thus, intrinsic biological differences exist between African American and European white breast tissue that might impact upon the incidence or etiology of breast cancer. We hypothesize that breast tissue from African American women will have a higher proportion of regenerative "stem" cells and/or their stem cells will have greater potency than those from European whites. We will flow cytometrically sort and quantify stem cells from established African American and European white breast epithelial cultures, clone them and assess them for potency using differentiation methods in culture.