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Origins of breast cancer subtypes and therapeutic implications

Breast cancers are composed of a variety of cell types with distinct morphologies and behaviors. It is not clear how this tumor heterogeneity comes about. This review summarizes and evaluates the current evidence for the cellular origins of breast cancer subtypes identified by different approaches such as immunological, genetic and gene-expression analysis. Breast cancer subtype is classified according to the tumor\\'s genetic expressions, for instance, basal-like: Estrogen Receptor (ER)-negative, Progesterone Receptor (PR)-negative, HER2-negative, cytokeratins (CKs) 5, 14 and 17-positive, luminal A: ER+ and/or PR+, HER2-, luminal B: ER+ and PR+, HER2+. Tumors from BRCA1 mutation carriers have been found to be frequently of the basal subtype, whereas BRCA2 tumors fall mainly within the luminal category. Growing knowledge about the normal breast cell types has led to the hypothesis that the subtypes of breast cancer might arise from mutations or genetic rearrangements that occur in different populations of stem cells and progenitor cells present in normal mammary gland. A subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. Since breast tumors may originate from cancer stem cells (CSCs), some cancer cells are resistant to current therapies. Consequently, inhibition of stem-cell self-renewal pathways should be explored because of the likelihood that residual stem cells might be resistant to current therapies. An understanding of this process will allow the development of more effective ways to treat and to prevent breast cancer. (Summarized by Dr. Naoko Abe, M.D.)

Andrew H Sims, Anthony Howell, Sacha J Howell and Robert B Clarke
Nature Clinical Practice Oncology September 2007 vol4 NO 9 516-525

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