Origins of breast cancer subtypes and therapeutic implications.
This Review summarizes and evaluates the current evidence for the cellular origins of breast cancer subtypes identified by different approaches such as histology, molecular pathology, genetic and gene-expression analysis. Emerging knowledge of the normal breast cell types has led to the hypothesis that the subtypes of breast cancer might arise from mutations or genetic rearrangements occurring in different populations of stem cells and progenitor cells. We describe the common distinguishing features of these breast cancer subtypes and explain how these features relate both to prognosis and to selection of the most appropriate therapy. Recent data indicate that breast tumors may originate from cancer stem cells. 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.
Sims
Andrew H
AH
Breast Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
Howell
Anthony
A
Howell
Sacha J
SJ
Clarke
Robert B
RB
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000145:classification* / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013234:Stem Cells / Q000473:pathology / Q000502:physiology; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D020845:Selective Estrogen Receptor Modulators; D000068878:Trastuzumab