Endocrine regulation of cancer stem cell compartments in breast tumors

Cancer cells within breast tumors exist within a hierarchy in which only a small and rare subset of cells is able to regenerate growths with the heterogeneity of the original tumor. These highly malignant cancer cells, which behave like stem cells for new cancers and are called "cancer stem cells" or CSCs, have also been shown to possess increased resistance to therapeutics, and represent the root cause underlying therapy failures, persistence of residual disease, and relapse. As >90% of cancer deaths are due to refractory tumors, identification of critical molecular drivers of the CSC-state would reveal vulnerabilities that can be leveraged in designing therapeutics that eradicate advanced disease and improve patient survival outcomes. An expanding and complex body of work has now described the exquisite susceptibility of CSC pools to the regulatory influences of local and systemic hormones. Indeed, breast CSCs express a plethora of hormonal receptors, which funnel hormonal influences over every aspect of breast neoplasia - be it tumor onset, growth, survival, invasion, metastasis, or therapy resistance - via directly impacting CSC behavior. This article is intended to shed light on this active area of investigation by attempting to provide a systematic and comprehensive overview of the available evidence directly linking hormones to breast CSC biology.