The Context for Ancestry in the Breast Cancer Stem Cell Paradigm

breast carcinogenesis, are intrinsically different in developmental potential in women of African-American (AA) ancestry and women of European white (EW) ancestry. Background. Breast cancer (BC) survival among AA is significantly lower than EW women, primarily because they are more likely to develop poorly prognostic disease. Since tumor type seems to be influenced by the cell type transformed, we measured the in vitro developmental potential of breast cultures from both groups of women. Methods. Our laboratory has developed a novel tissue engineering system for human breast tissue that allows for unusually long-term ( > 3 months) establishment of normal primary cultures that begin as 3-dimensional “epispheres," structures made up of 40-100 epithelial cells. These epispheres spontaneously differentiate into complex organotypic branching ducts and lobules. Results. 48 renewable explant cultures were established from non-diseased breast reduction mammoplasty tissues, including 12 (25%) from socioeconomically matched AA women, and allowed to differentiate in vitro. After multivariate analysis, a robust and significant model for the timing of in vitro ductal formation (P = 0.005) involved only the ancestry of the donor and her height. Applied to the validation set, the sensitivity of this model was 100% and the specificity 66.7%. Conclusion. Intrinsic biological differences exist between AA and EW breast tissue that is demonstrated by the ability of these cultures to differentiate. Since factors affecting breast differentiation also affect breast cancer incidence, AA women may have an inherently higher risk of 58 developing this disease. Grants. This study was partially supported by grants from the DOD CDBCRP and Susan G. Komen for the Cure.