Clinical implications of breast cancer stem cells: A review

Cancer stem cells (CSCs) are a small population of cells within a tumor which perform stem cell like functions including self-renewal, differentiation and initiation. This narrative review aims to provide an overview of the role of CSCs in resistance to standard treatment and metastasis in breast cancer, potential treatment strategies including latest clinical trials, and the clinical implications for CSCs in the management of breast cancer. The most established breast CSC markers (CD44+/CD24- and ALDH1) are most prevalent in basal-like cancers, the most aggressive subtype of breast cancer. The most implicated CSC pathways include Hedgehog, Notch, CXCR1, and Wnt. Previous phase I/II trials targeting these pathways associated with breast CSCs have shown mixed results; no CSC-specific drug has reached phase III trial in breast cancer. To maximize the potential benefit of CSC-targeted therapy, it would be important to select or enrich patients with CSC markers or CSC-associated pathway activation. It would also be critical to develop combination strategies that overcome plasticity and/or immune invasion, and preferentially destroy CSCs with limited impact on healthy stem cells. Overall, breast CSCs may have greater clinical implications but require further research and development to realize their full clinical potential.