Abstract C26: Analysis of stem cell number & potency in African-American breast tissue

Breast cancer (BC) survival among African-American (AA) women 5 years after initial diagnosis is only 74%, significantly lower than the 88% survival observed in women of European white (EW) ancestry. The differences in outcomes have been attributed to the greater prevalence of Triple Negative Breast Cancer (TNBC) in AA women and, indeed, stage for stage, TNBC is more lethal than luminal type BCs. Why AA women are more likely to develop TNBC remains a major question. In the past, disparities in BC outcomes were frequently attributed to socioeconomic factors, but increasing data suggests that it is based on intrinsic differences in AA breast tissue compared with EW. Risk factors for BC have been extensively investigated and include elements impacting breast differentiation and development, including timing of thelarche and menarche, as well as timing and number of pregnancies. Breast formation (thelarche) occurs in AA girls 2 years earlier than EW girls in the US. The purpose of this study was to better understand the etiology of premature thelarche and, by extension, BC etiology in AA women. We utilized a unique tissue engineering system that our laboratory has developed for culture of human breast epithelial cells, both normal and malignant. This system allows for long-term (>3 months) growth of normal primary epithelial cell cultures. These cultures form 3-dimensional “epispheres,” made up of 40-100 epithelial cells, which can then differentiate into organotypic branching ducts and lobules. We have established explant cultures of normal breast epithelial cells from 48/48 non-diseased women undergoing breast reduction mammoplasty. Twelve of these (25%) were AA women socioeconomically matched with the EW women. Analysis of these cultures resulted in a significant multivariate model for the timing of ductal formation (P = 0.005) involving only the ancestry of the donor and her height. Thus, intrinsic biological differences exist between AA and EW breast tissue that might impact upon the incidence or etiology of BC. We hypothesized that stem cells from AA women would be present in higher proportions or alternatively demonstrate higher potency than EW. Breast epithelial stem cells were defined by the absence of CD24 antigen and the presence of CD44 and CD49f antigens on the cell surface using quantitative flow cytometric analysis. Cloning efficiency, defined as sorted single cells that grew into colonies, was quantified as a percentage of the total cells sorted and verified microscopically. Potency, defined as colonies that exhibited multiple cell types, was quantified as a percentage of the total cloning efficiency. Our results indicate that AA samples, on average, contained 48.4% breast stem cells, while EW samples manifested a significantly smaller proportion, only 7.2% (P = 0.018). Cloning efficiency and potency analyses are currently ongoing. In summary AA women display higher proportions of stem cells in normal breast tissues relative to EW, which may be pertinent to premature thelarche and by extension, triple negative breast cancer etiology. Citation Format: Omar Ibrahim, Stephen G. Grant, Nicole T. Myers, Amie B. Courtney, Nancy A. lalanne, Jean J. Latimer. Analysis of stem cell number & potency in African-American breast tissue. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C26.