BRCA1 and breast cancer: To evaluate whether hyperactive RANKL/RANK signaling might be essential for the generation and maintenance of CSC-like cellular states in BRCA1 haploinsufficient cells, we took advantage of the functional ability of breast cancer cell lines to display a subpopulation of cells with CSC-like properties defined experimentally by their ability to to self-renew and form anchorage-independent multicellular microtumors or “mammospheres” in non-adherent, non-differentiating conditions in vitro at low frequency [20, 21].