title: High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients.
abstract: BACKGROUND
  Circulating tumor cells (CTCs) are a prognostic marker in metastatic breast cancer, but comparisons with serum tumor markers (CA 15-3, carcinoembryonic antigen and lactate dehydrogenase) variations are needed.
  
  
  METHODS
  CTCs were counted with CellSearch® at baseline, before cycle 2 (C2) and cycle 3 or 4 (C3/4) in 267 metastatic breast cancer patients on first-line chemotherapy with/without targeted therapy.
  
  
  RESULTS
  Baseline CTC detection rate was 65% with ≥1 CTC/7.5 ml threshold and 44% with ≥5 CTC/7.5 ml and was independent of subtypes (luminal, triple negative, human epithelial growth factor receptor 2 (HER2)+). CTCs were associated with tumor markers, bone/liver involvement, tumor burden and performance status. CTC detection ≥1 CTC/7.5 ml was a strong prognostic factor for progression-free survival (PFS), P < 0.0001. Threshold of CTC ≥5 was statistically significant for PFS and overall survival (OS), P = 0.03 on multivariate analysis. Among patients with ≥5 CTC/7.5 ml at baseline, 50% had <5 CTC/7.5 ml at C2. Changes were correlated with both PFS and OS (P < 0.0001). All patients receiving anti-HER2 therapy had <5 CTC/7.5 ml after three cycles of treatment.
  
  
  CONCLUSIONS
  This is the largest prospective series validating the prognostic value of CTC independently from serum tumor marker. Elevated CTCs before C2 are an early predictive marker of poor PFS and OS, which could be used to monitor treatment benefit. CTC decrease under treatment seems stronger with targeted therapy.
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris; Université Paris Descartes, Paris. Electronic address: jean-yves.pierga@curie.net.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Pierga
authors.affiliation: Department of Biostatistics, Institut Curie, Paris.
authors.forename: D
authors.initials: D
authors.lastname: Hajage
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon.
authors.forename: T
authors.initials: T
authors.lastname: Bachelot
authors.affiliation: Department of Medical Oncology, Institut Gustave Roussy, Villejuif.
authors.forename: S
authors.initials: S
authors.lastname: Delaloge
authors.affiliation: Department of Medical Oncology, Institut Curie, Hôpital René Huguenin, Saint Cloud.
authors.forename: E
authors.initials: E
authors.lastname: Brain
authors.affiliation: Department of Medical Oncology, Centre René Gauducheau, Saint Herblain.
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris.
authors.forename: V
authors.initials: V
authors.lastname: Diéras
authors.affiliation: Department of Biostatistics, Institut Curie, Paris.
authors.forename: E
authors.initials: E
authors.lastname: Rolland
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris.
authors.forename: L
authors.initials: L
authors.lastname: Mignot
authors.affiliation: Hematology laboratory, Institut Curie, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Mathiot
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris; Université Paris Descartes, Paris.
authors.forename: F-C
authors.initials: FC
authors.lastname: Bidard
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000187:drug effects*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor