Evolving views of breast cancer stem cells and their differentiation states

Cellular heterogeneity is a prominent characteristic of breast cancers, and accumulating evidence indicates that variability in the differentiation state of tumor cells contributes to this phenomenon. Breast cancers are among the tumor types in which the existence of cancer stem cells has been widely supported, and specific markers, including CD44/CD24 and ALDH1, have been consistently used to identify such cells. Recent studies have revealed the potential for dynamic bidirectional transitions of breast cancer cells between differentiated and stem-like phenotypes. In addition, the potential importance of intermediate states along differentiation axes, including the epithelial-to-mesenchymal transition and the basal–luminal differentiation axis, has emerged. These findings provide a view of breast cancer stem cells that departs from the traditional unidirectional hierarchical model, as well as new insights into the mechanisms by which differentiation events contribute to breast cancer biology. Herein we discuss these advances.