title: Systematic analysis of in vitro chemosensitivity and mib-1 expression in molecular breast cancer subtypes.
abstract: BACKGROUND
  Molecular breast cancer subgroups show differences with regard to prognosis and response to chemotherapy. In vitro chemotherapy sensitivity and resistance assays (CSRAs) are a means to directly evaluate tumour cell response to a given drug.
  
  
  METHODS
  Using tissue microarray (TMA) analysis, 550 invasive breast cancers were investigated for the expression of oestrogen receptor (ER), progesterone receptor (PR), vimentin, Ck5, Ck14, Ck19, HER2 and Mib-1/Ki-67. All carcinomas were subjected to in vitro CSRA analysis using three separate chemotherapy combinations. In vitro chemotherapy sensitivity was established using an adenosine triphosphate (ATP) bioluminescence assay. Results of immunohistochemical staining and in vitro response were correlated.
  
  
  RESULTS
  Mib-1 expression was associated with sensitivity against Paclitaxel/Epirubicin (p = 0.014) and Docetaxel/Epirubicin (p = 0.014). Mib-1 expression was positively/negatively correlated with expression of basal/luminal markers, respectively. Hierarchical clustering revealed three subtypes, resembling luminal, basal-like and HER2-like breast cancer subtypes. In vitro response for Paclitaxel/Epirubicin was most frequently observed for cases in the basal category (40.3%) compared to HER2-like (25.8%) and luminal cases (28.6%). In multivariate analysis expression of Mib-1 was not a significant independent predictor of in vitro response to chemotherapy.
  
  
  CONCLUSIONS
  Breast cancer molecular subclasses show differences regarding in vitro chemotherapy sensitivity. These may in part explain differences observed between breast cancer molecular subtypes in vivo.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Muenster, Muenster, Germany. liedtkec@ukmuenster.de
authors.forename: Cornelia
authors.initials: C
authors.lastname: Liedtke
authors.forename: Jens
authors.initials: J
authors.lastname: Packeisen
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: Ulf
authors.initials: U
authors.lastname: Vogt
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kiesel
authors.forename: Christian
authors.initials: C
authors.lastname: Kersting
authors.forename: Eberhardt
authors.initials: E
authors.lastname: Korsching
authors.forename: Burkhard
authors.initials: B
authors.lastname: Brandt
authors.forename: Horst
authors.initials: H
authors.lastname: Buerger
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen