Cell of Origin of Breast Cancer: An Updated Hypothesis Merging Epidemiological Data with Molecular Biology

Two different hypotheses about cell of origin of breast cancer have been proposed. One theory states that breast cancer originates from an epithelial stem cell and subsequent genetic changes determine the phenotype, while another hypothesis postulates that breast cancer could originate from different cells, both stem cells and progenitor cells. Therefore, the phenotype in the latter situation is partly dependent on the differentiation of the epithelial cell of origin. Based initially on epidemiological data new research for instance gene expression arrays and gene transfection models supports the theory postulating that tumour biology of a breast cancer at least partly reflects the biology of the tissue/epithelial cell of origin at the time of initiation. It may be that the different theories actually not oppose each other and that tumours may develop from different precursor cells such as sometimes from a stem cell and sometimes from differently developed progenitor cells. The type of the mutations acquired, and/or the differentiation potential of the cancer cells, and the cell of origin are likely to decide whether a tumor follows a Cancer Stem Cell (CSC) model.However, there are still unanswered questions that need to be addressed by further research to especially understand the hierarchy of differentiation of normal and tumour tissue