A schematic summary of breast cancer heterogeneity. According to the cancer stem cell hypothesis, breast cancer is driven by a limited number of cancer-initiating cells. The progeny of these cells can either progress along the differentiation pathway or remain blocked in a proliferation state. Molecular subtypes, such as basal and luminal, differ by their degree of proliferation and differentiation (as shown by the red and blue wedges). They represent stages that can be recognized along a continuum (shown by the dashed line) from progenitor-like proliferative tumors (basal subtype) to luminal differentiated tumors. Breast cancer heterogeneity is due both to different cells of origin and to alterations in the genome and epigenome. The demonstration by the Miska and Caldas groups of a different distribution of miRNAs among subtypes  and of variations in genome instability and heterogeneity of estrogen receptor (ER)-negative tumors  (arrows) contribute to the understanding and classification of breast cancers.