title: Circulating tumor cell analysis in metastatic triple-negative breast cancers.
abstract: OBJECTIVE
  Recent developments in rare-cell technology have led to improved blood-based assays that allow for the reliable detection, enumeration, and more recently, genomic profiling of circulating tumor cells (CTC). We evaluated two different approaches for enumeration of CTCs in a prospective therapeutic study of patients with metastatic triple-negative breast cancer (TNBC).
  
  
  METHODS
  The CellSearch system, a commercially available and U.S. Food and Drug Administration (FDA)-cleared assay for CTC enumeration, and IE/FC, an alternative method using EPCAM-based immunomagnetic enrichment and flow cytometry that maintains cell viability, were used to enumerate CTCs in the blood of patients with metastatic TNBC. CTC numbers were assessed at baseline and 7 to 14 days after initiation of therapy with cetuximab ± carboplatin in a phase II multicenter clinical trial (TBCRC 001).
  
  
  RESULTS
  CTC numbers from two methods were significantly correlated at baseline (r = 0.62) and at 7 to 14 days (r = 0.53). Baseline CTCs showed no association with time-to-progression (TTP), whereas CTCs at 7 to 14 days were significantly correlated with TTP (CellSearch P = 0.02; IE/FC P = 0.03). CTCs at both time points were significantly associated with overall survival (OS) [CellSearch: baseline (P = 0.0001) and 7 to 14 days (P < 0.0001); IE/FC: baseline (P = 0.0009) and 7 to 14 days (P = 0.0086)].
  
  
  CONCLUSIONS
  Our findings demonstrate that CTC enumeration by two different assays was highly concordant. In addition, results of both assays were significantly correlated with TTP and OS in patients with TNBC. The IE/FC method is also easily adapted to isolation of pure populations of CTCs for genomic profiling.
authors.affiliation: University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
authors.forename: Mark Jesus M
authors.initials: MJ
authors.lastname: Magbanua
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
authors.affiliation: University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
authors.forename: Amy
authors.initials: A
authors.lastname: DeLuca
authors.affiliation: University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Hwang
authors.affiliation: University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
authors.forename: Janet H
authors.initials: JH
authors.lastname: Scott
authors.affiliation: Baylor University College of Medicine, Houston, Texas.
authors.forename: Mothaffar F
authors.initials: MF
authors.lastname: Rimawi
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Mayer
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: P Kelly
authors.initials: PK
authors.lastname: Marcom
authors.affiliation: Georgetown University, Washington, District of Columbia.
authors.forename: Minetta C
authors.initials: MC
authors.lastname: Liu
authors.affiliation: Laura & Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.affiliation: University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
authors.forename: John W
authors.initials: JW
authors.lastname: Park
authors.affiliation: University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California. hrugo@medicine.ucsf.edu.
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
mesh_terms: D002452:Cell Count; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D063868:Patient Outcome Assessment; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality