title: Prognostic relevance of viable circulating tumor cells detected by EPISPOT in metastatic breast cancer patients.
abstract: BACKGROUND
  Detection of circulating tumor cells (CTC) in breast cancer patients is currently performed in many clinical trials, using different technologies, in particular the EpCAM-dependent CellSearch® system. The purpose of this study was to investigate the incidence and prognostic relevance of viable CTC in a large cohort of metastatic breast cancer (MBC) patients.
  
  
  METHODS
  A total of 254 MBC patients were enrolled in a prospective multicenter study at first diagnosis of metastatic disease or disease progression (before the start of a new treatment regimen). After EpCAM-independent enrichment, viable CTC releasing cytokeratin-19 as an epithelial cell marker were detected in the peripheral blood by an EPISPOT assay, and the Food and Drug Administration cleared CellSearch was used as the reference method.
  
  
  RESULTS
  Using the EPISPOT assay, CTC were detected in 59% of MBC patients. The overall survival (OS) was linked with the CTC status measured by EPISPOT (P = 0.0191), which allowed stratification of MBC patients in low- and high-risk groups. This stratification could be improved by addition of the CTC status assessed by the CellSearch system. In multivariate Cox proportional-hazards regression analysis, the 3 methods used to determine the level of CTC (EPISPOT, CellSearch, and combination of EPISPOT/CellSearch) were compared by the Bayesian information criterion method. Interestingly, the combination of the EPISPOT and CellSearch assays was the strongest predictor of OS (hazard ratio, 22.6; 95% CI, 2.8-184.08).
  
  
  CONCLUSIONS
  This is the first study in which CTC detection using the EPISPOT assay was evaluated on a large cohort of MBC patients, showing prognostic relevance of the presence of viable CTC.
authors.affiliation: University Medical Centre, Saint-Eloi Hospital, Institute of Research in Biotherapy, Department of Cellular and Tissular Biopathology of tumors, Laboratory of Rare Human Circulating Cells, Montpellier, France;
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Ramirez
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Mattea
authors.initials: M
authors.lastname: Orsini
authors.forename: Laure
authors.initials: L
authors.lastname: Cayrefourcq
authors.forename: Thierry
authors.initials: T
authors.lastname: Maudelonde
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Catherine
authors.initials: C
authors.lastname: Alix-Panabières
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000175:diagnosis*; D019963:Clinical Chemistry Tests / Q000295:instrumentation; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D012015:Reference Standards
chemical_list: D014408:Biomarkers, Tumor