title: Detection and prognostic significance of circulating tumour cells in patients with metastatic breast cancer according to immunohistochemical subtypes.
abstract: BACKGROUND
  The enumeration of circulating tumour cells (CTCs) with the EpCAM-based CellSearch system has prognostic significance in patients with metastatic breast cancer (MBC). The aim of this study was to explore potential differences in the detection and prognostic significance of CTCs in MBC according to immunohistochemical subtypes of breast cancer.
  
  
  METHODS
  CellSearch CTC counts were obtained from 154 MBC patients before first-line systemic treatment between November 2007 and August 2012. Patients were categorised in five subgroups according to immunohistochemical surrogate definitions of intrinsic subtypes in breast cancer based on hormone receptor status, HER2/neu status and histological grade. Differences in progression-free (PFS) and overall survival (OS) were assessed relative to the cut-off value of ≥5 CTCs per 7.5 ml blood.
  
  
  RESULTS
  No significant differences were observed in the absolute CTC counts (P=0.120) or in CTC positivity rates according to ≥1 and ≥5 CTCs per 7.5 ml blood detection thresholds (P=0.165 and P=0.651, respectively) between immunohistochemical subtypes. However, very high CTC counts, defined as ≥80 CTCs per 7.5 ml, were observed more frequently in patients with Luminal A and triple negative (TN) breast cancer (P=0.024). In the total study population, the presence of ≥5 CTCs was the single most significant prognostic factor for both PFS and OS in multivariate analysis (P<0.001). A more limited prognostic impact, not reaching statistical significance, was observed in patients with HER2-positive disease as opposed to patients with Luminal A, Luminal B-HER2-negative and TN disease.
  
  
  CONCLUSIONS
  The detection of EpCAM+CTCs was not clearly associated with any of the immunohistochemical subtypes of breast cancer in patients with MBC before first-line treatment. Potentially clinically relevant differences were however observed at very high CTC counts. Furthermore, our data suggest a lower prognostic significance of CTC evaluation in HER2-positive patients with MBC.
authors.affiliation: 1] Translational Cancer Research Unit, Oncology Centre GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, B-2610 Antwerp, Belgium [2] Department of Oncology, University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: D J E
authors.initials: DJ
authors.lastname: Peeters
authors.affiliation: Translational Cancer Research Unit, Oncology Centre GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, B-2610 Antwerp, Belgium.
authors.forename: P-J
authors.initials: PJ
authors.lastname: van Dam
authors.affiliation: Translational Cancer Research Unit, Oncology Centre GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, B-2610 Antwerp, Belgium.
authors.forename: G G M
authors.initials: GG
authors.lastname: Van den Eynden
authors.affiliation: Translational Cancer Research Unit, Oncology Centre GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, B-2610 Antwerp, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Rutten
authors.affiliation: Translational Cancer Research Unit, Oncology Centre GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, B-2610 Antwerp, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Wuyts
authors.affiliation: Translational Cancer Research Unit, Oncology Centre GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, B-2610 Antwerp, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Pouillon
authors.affiliation: Department of Oncology, University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Department of Pathology, University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Pauwels
authors.affiliation: Translational Cancer Research Unit, Oncology Centre GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, B-2610 Antwerp, Belgium.
authors.forename: S J
authors.initials: SJ
authors.lastname: Van Laere
authors.affiliation: 1] Translational Cancer Research Unit, Oncology Centre GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, B-2610 Antwerp, Belgium [2] Department of Oncology, University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: P A
authors.initials: PA
authors.lastname: van Dam
authors.affiliation: Translational Cancer Research Unit, Oncology Centre GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, B-2610 Antwerp, Belgium.
authors.forename: P B
authors.initials: PB
authors.lastname: Vermeulen
authors.affiliation: Translational Cancer Research Unit, Oncology Centre GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, B-2610 Antwerp, Belgium.
authors.forename: L Y
authors.initials: LY
authors.lastname: Dirix
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D002452:Cell Count / Q000379:methods; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases