ESR1 and neoplasm: Al-Hajj et al. (2003) were the first to show that tumor-initiating cells were capable of recapitulating the original tumor phenotype when transplanted into immunodeficient mice. In vitro functional assays for BC stem cell (BCSC) activity include aldehyde dehydrogenase 1 (ALDH1) enzyme activity and the capacity to form clonogenic mammospheres in suspension culture (Ginestier et al., 2007). It has been demonstrated that the BCSC population is ER negative/low and resistant to the direct effects of endocrine therapy (Simões et al., 2011; Harrison et al., 2013; Piva et al., 2014).