title: Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
abstract: BACKGROUND
  Distant recurrences after antineoplastic treatment remain a serious problem for breast cancer clinical management, which threats patients' life. Systemic therapy is administered to eradicate cancer cells from the organism, both at the site of the primary tumor and at any other potential location. Despite this intervention, a significant proportion of breast cancer patients relapse even many years after their primary tumor has been successfully treated according to current clinical standards, evidencing the existence of a chemoresistant cell subpopulation originating from the primary tumor.
  
  
  RESULTS
  To identify key molecules and signaling pathways which drive breast cancer chemoresistance we performed gene expression analysis before and after anthracycline and taxane-based chemotherapy and compared the results between different histopathological response groups (good-, mid- and bad-response), established according to the Miller & Payne grading system. Two cohorts of 33 and 73 breast cancer patients receiving neoadjuvant chemotherapy were recruited for whole-genome expression analysis and validation assay, respectively. Identified genes were subjected to a bioinformatic analysis in order to ascertain the molecular function of the proteins they encode and the signaling in which they participate. High throughput technologies identified 65 gene sequences which were over-expressed in all groups (P ≤ 0·05 Bonferroni test). Notably we found that, after chemotherapy, a significant proportion of these genes were over-expressed in the good responders group, making their tumors indistinguishable from those of the bad responders in their expression profile (P ≤ 0.05 Benjamini-Hochgerg`s method).
  
  
  CONCLUSIONS
  These data identify a set of key molecular pathways selectively up-regulated in post-chemotherapy cancer cells, which may become appropriate targets for the development of future directed therapies against breast cancer.
authors: Department of Oncology, Complejo Hospitalario de Jaen, Jaen, Spain. laura.vera@genyo.es
authors: Laura
authors: L
authors: Vera-Ramirez
authors: Pedro
authors: P
authors: Sanchez-Rovira
authors: Cesar L
authors: CL
authors: Ramirez-Tortosa
authors: Jose L
authors: JL
authors: Quiles
authors: McArmen
authors: M
authors: Ramirez-Tortosa
authors: Jose A
authors: JA
authors: Lorente
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D015398:Signal Transduction / Q000235:genetics; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane