title: PAM50 breast cancer intrinsic subtypes and effect of gemcitabine in advanced breast cancer patients.
abstract: BACKGROUND
  In vitro studies suggest basal breast cancers are more sensitive to gemcitabine relative to other intrinsic subtypes. The main objective of this study was to use specimens from a randomized clinical trial to evaluate whether the basal-like subtype identifies patients with advanced breast cancer who benefit from gemcitabine plus docetaxel (GD) compared to single agent docetaxel (D).
  
  
  METHODS
  From patients randomly assigned to GD or D, RNA was isolated from archival formalin-fixed, paraffin-embedded primary breast tumor tissue and used for PAM50 intrinsic subtyping by NanoString nCounter. Statistical analyses were prespecified as a formal prospective-retrospective clinical trial correlative study. Using time to progression (TTP) as primary endpoint, overall survival (OS) and response rate as secondary endpoints, relationships between subtypes and outcome after chemotherapy were analyzed by the Kaplan-Meier method, and Cox proportional hazards regression models. Data analysis was performed independently by the Danish Breast Cancer Cooperative Group (DBCG) statistical core and all statistical tests were two-sided.
  
  
  RESULTS
  RNA from 270 patients was evaluable; 84 patients (31%) were classified as luminal A, 97 (36%) luminal B, 43 (16%) basal-like, and 46 (17%) as HER2-enriched. PAM50 intrinsic subtype was a significant independent prognostic factor for both TTP (p=0.014) and OS (p=0.0003). Response rate was not different by subtype, and PAM50 was not a predictor of TTP by treatment arm. PAM50 was however a highly significant predictor of OS following GD compared to D (pinteraction=0.0016). Patients with a basal-like subtype had a significant reduction in OS events [hazard ratio (HR)=0.29, 95% confidence interval (CI)=0.15-0.57; pinteraction=0.0006].
  
  
  CONCLUSIONS
  A significantly improved and clinically important prolongation of survival was seen from the addition of gemcitabine to docetaxel in advanced basal-like breast cancer patients.
authors.affiliation: Department of Pathology, Herlev University Hospital , Herlev , Denmark.
authors.forename: Charlotte L T
authors.initials: CL
authors.lastname: Jørgensen
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: Karsten D
authors.initials: KD
authors.lastname: Bjerre
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Liu
authors.forename: Brett
authors.initials: B
authors.lastname: Wallden
authors.forename: Eva
authors.initials: E
authors.lastname: Balslev
authors.forename: Dorte L
authors.initials: DL
authors.lastname: Nielsen
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis*; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D012333:RNA, Messenger; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine