title: Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival.
abstract: OBJECTIVE
  We reported previously that >or=5 circulating tumor cells (CTC) in 7.5 mL blood at baseline and at first follow-up in 177 patients with metastatic breast cancer (MBC) were associated with poor clinical outcome. In this study, additional follow-up data and CTC levels at subsequent follow-up visits were evaluated.
  
  
  METHODS
  CTCs were enumerated in 177 MBC patients before the initiation of a new course of therapy (baseline) and 3 to 5, 6 to 8, 9 to 14, and 15 to 20 weeks after the initiation of therapy. Progression-free survival (PFS) and overall survival (OS) times were calculated from the dates of each follow-up blood draw. Kaplan-Meier plots and survival analyses were done using a threshold of >or=5 CTCs/7.5 mL at each blood draw.
  
  
  RESULTS
  Median PFS times for patients with <5 CTC from each of the five blood draw time points were 7.0, 6.1, 5.6, 7.0, and 6.0 months, respectively. For patients with >or=5 CTC, median PFS from these same time points was significantly shorter: 2.7, 1.3, 1.4, 3.0, and 3.6 months, respectively. Median OS for patients with <5 CTC from the five blood draw time points was all >18.5 months. For patients with >or=5 CTC, median OS from these same time points was significantly shorter: 10.9, 6.3, 6.3, 6.6, and 6.7 months, respectively. Median PFS and OS times at baseline and up to 9 to 14 weeks after the initiation of therapy were statistically significantly different.
  
  
  CONCLUSIONS
  Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients.
authors.affiliation: Department of Internal Medicine and the Comprehensive Cancer Center, University of Michigan Health and Hospital System, Ann Arbor, Michigan 48109, USA. hayesdf@umich.edu
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: G Thomas
authors.initials: GT
authors.lastname: Budd
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
authors.forename: Alison
authors.initials: A
authors.lastname: Stopeck
authors.forename: M Craig
authors.initials: MC
authors.lastname: Miller
authors.forename: Jeri
authors.initials: J
authors.lastname: Matera
authors.forename: W Jeffrey
authors.initials: WJ
authors.lastname: Allard
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Doyle
authors.forename: Leon W W M
authors.initials: LW
authors.lastname: Terstappen
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome