Breast Stem Cell Markers and Tumor Stem Cells in BRCA1, BRCA2 and Non-BRCA 1/2 Women

It is believed that certain breast tumors originate in either a breast stem or progenitor cell. Notably, tumors that arise in women carrying a BRCA1 gene mutation often exhibit a basal phenotype that may reflect their origin in the breast stem cell. We therefore hypothesized that the breast stem cell pool is aberrant in breast tissue of BRCA1 or BRCA2carriers versus noncarriers and that it becomes progressively and distinctively expanded in older carriers. To evaluate this concept, we performed a pilot study in which we obtained archival samples from breast tissue from the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer kConFab. We first derived and analyzed subpopulations of breast tissue for the expression of putative stem cell markers and investigated means to derive short-term in vitro cultures. Our preliminary findings indicate that it is possible to identify distinct subpopulations in normal breast tissue and tissue derived from BRCAmutations carriers. These studies our now being extended to study putative stem and progenitor populations using reduction mammoplasties and prophylatic mastectomy specimens.