Stem Cells in Breast Development and Cancer

The concept of the stem cell of origin for cancers was first proposed more than 100 years ago. In this theoretical model, certain cells with self-renewal capacity would form tumors from “embryonic rests.” More evidence has accumulated since that time as a result of extensive research that strongly supports the cancer stem cell (CSC) hypothesis, suggesting the existence of self-renewing cells that generate heterogenous populations of cells within the tumor mass. The preponderance of evidence now suggests that the majority of cancers are hierarchically organized and sustained by a population of cells that display stem cell properties—CSCs. As is the case for normal tissue stem cells, CSCs are able to self-renew and differentiate, generating cells that comprise the tumor bulk. Furthermore, preclinical and clinical studies demonstrate that CSCs mediate tumor metastasis and contribute to resistance to chemotherapy and radiation therapy. The CSC hypothesis has fundamental biological and clinical implications that are discussed in detail in this chapter.