title: Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer.
abstract: BACKGROUND
  The presence of ≥5 circulating tumor cells (CTCs) in 7.5 ml blood is a poor prognostic marker in metastatic breast cancer (MBC). However, the role of human epidermal growth factor receptor 2 (HER2) status in CTCs is not known.
  
  
  METHODS
  We prospectively assessed the prognostic value of this parameter for patients with MBC who started a new line of systemic therapy. The CTC count (≥5 or <5) and the HER2 status in CTCs at the initiation of the therapy and 3-4 weeks later (first follow-up) were determined.
  
  
  RESULTS
  The median follow-up time of the 52 enrolled patients was 655.0 days (18-1,275 days). HER2-positive CTCs were present in 14 of the 52 patients (26.9%) during the study period. Eight of 33 patients (24.2%) with HER2-negative primary tumors had HER2-positive CTCs during the study period. At first follow-up, patients with HER2-positive CTCs had significantly shorter progression-free (n = 6; P = 0.001) and overall (P = 0.013) survival than did patients without HER2-positive CTCs (n = 43) in log-rank analysis. In multivariate analysis, HER2-positive CTCs at first follow-up (P = 0.029) and the number of therapies patients received before this study (P = 0.006) were independent prognostic factors in terms of progression-free survival. The number of therapies (P = 0.001) and a count of ≥5 CTCs (P = 0.043) at baseline were independent prognostic factors in terms of overall survival.
  
  
  CONCLUSIONS
  We showed that HER2 status in CTCs may be a prognostic factor for MBC. Well-powered prospective studies are necessary to determine the potential role of HER2-targeted therapies for patients with HER2-positive CTCs and HER2-negative primary tumors.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Seigo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tokuda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shimoda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshida
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ota
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy; D002452:Cell Count; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human