A new paradigm for African American breast cancer involving stem cell differentiation.

Abstract

Abstract Abstract #5051 Background: African American (AA) women have a higher incidence of breast cancer (BC) than white women before age 40, and are more likely to die from BC at every age. These differences are often attributed to socio-economic factors, however, there may be intrinsic biological differences in the breast tissue of AA and white women. For example, triple negative breast tumors are more prevalent in AA women than in non-Hispanic white women, although neither population is monolithic in its breast cancer phenotypes. We hypothesis that intrinsic biological differences between women of AA and European-white ancestry might be revealed by differences in growth and differentiation in vitro, reflecting underlying differences in the proportions and/or potency of breast epithelial stem cells.
 Methods: Our laboratory has developed a novel tissue engineering system for Human Mammary Epithelial Cells (HMEC), both normal and malignant. This system allows for long-term establishment of non-diseased primary cultures that begin as 3-dimensional attached “epispheres”, that are structures made up of 40-100 epithelial cells. These non-diseased epispheres subsequently differentiate into functional, organotypic branching ducts and lobules that demonstrate ESA and CK -18,-19 staining, lumen, polarized nuclei, desmosomes, microvilli on apical surfaces and casein secretion.
 Results: We have established primary HMEC cultures from 36/36 breast reduction mammoplasty tissues, including 9 AA donors matched in socioeconomic status. We have found: 1) The more children a woman had, the less likely her breast tissue was to form ductal structures in vitro. This finding is consistent with the idea that lactational differentiation decreases the number of pluripotent stem cells in the breast. 2) Pre-menopausal breast tissue was more likely to form ductal structures than post-menopausal tissue. 3) Race was a modifying factor in the ability to form ductal architecture in culture, significantly affecting the rate of differentiation. Putative mammary stem cells were analyzed by flow cytometry (CD44+, CD24-, MUC1-, α6 integrin+) and cloning. Stem cell proportions varied widely (range 0.5-15%), with no obvious association with race.
 Discussion: One interpretation of the hormonal risk factors for BC involves the susceptibility of undifferentiated breast tissue to transformation. In other systems, especially the gonads, interference with terminal differentiation is also associated with susceptibility to transformation. If AA breast tissue has more robust differentiation potential than that of white women, it may also contain stem cells more likely to transform into an aggressive tumor type. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5051.