title: Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer.
abstract: Although unequivocal evidence has shown the prognostic relevance of circulating tumor cells (CTC) in the peripheral blood of patients with metastatic breast cancer, less evidence is available for the prognostic relevance of CTCs at the time of primary diagnosis.
  
  
  
  We conducted a pooled analysis of individual data from 3,173 patients with nonmetastatic (stage I-III) breast cancer from five breast cancer institutions. The prevalence and numbers of CTCs were assessed at the time of primary diagnosis with the FDA-cleared CellSearch System (Janssen Diagnostics, LLC). Patient outcomes were analyzed using meta-analytic procedures, univariate log-rank tests, and multivariate Cox proportional hazard regression analyses. The median follow-up duration was 62.8 months.
  
  
  
  One or more CTCs were detected in 20.2% of the patients. CTC-positive patients had larger tumors, increased lymph node involvement, and a higher histologic tumor grade than did CTC-negative patients (all P < 0.002). Multivariate Cox regressions, which included tumor size, nodal status, histologic tumor grade, and hormone receptor and HER2 status, confirmed that the presence of CTCs was an independent prognostic factor for disease-free survival [HR, 1.82; 95% confidence interval (CI), 1.47-2.26], distant disease-free survival (HR, 1.89; 95% CI, 1.49-2.40), breast cancer-specific survival (HR, 2.04; 95% CI, 1.52-2.75), and overall survival (HR, 1.97; 95% CI, 1.51-2.59).
  
  
  
  In patients with primary breast cancer, the presence of CTCs was an independent predictor of poor disease-free, overall, breast cancer-specific, and distant disease-free survival. Clin Cancer Res; 22(10); 2583-93. ©2016 AACR.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany. wolfgang.janni@uniklinik-ulm.de.
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Janni
authors.affiliation: Department of Gynecology and Obstetrics, Ludwig-Maximilians University of Munich, Munich, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
authors.affiliation: Medical Cell BioPhysics Group, University of Twente, Enschede, the Netherlands.
authors.forename: Leon W M M
authors.initials: LW
authors.lastname: Terstappen
authors.affiliation: Department of Medical Oncology, Institut Curie, Université Paris Descartes, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
authors.affiliation: Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Florin-Andrei
authors.initials: FA
authors.lastname: Taran
authors.affiliation: Department of Gynecology and Obstetrics, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hall
authors.affiliation: Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Marco R
authors.initials: MR
authors.lastname: de Groot
authors.affiliation: Department of Medical Oncology, Institut Curie, Université Paris Descartes, Paris, France.
authors.forename: François-Clement
authors.initials: FC
authors.lastname: Bidard
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
authors.forename: Thomas W P
authors.initials: TW
authors.lastname: Friedl
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.affiliation: Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Sara Y
authors.initials: SY
authors.lastname: Brucker
authors.affiliation: Department of Tumor Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor