title: Circulating tumor cells in immunohistochemical subtypes of metastatic breast cancer: lack of prediction in HER2-positive disease treated with targeted therapy.
abstract: BACKGROUND
  Circulating tumor cells (CTCs) are associated with inferior prognosis in metastatic breast cancer (MBC). We hypothesized that the relationship between CTCs and disease subtype would provide a better understanding of the clinical and biologic behavior of MBC.
  
  
  METHODS
  We retrospectively analyzed 517 MBC patients treated at a single institution. Subtypes of primary tumors were analyzed by immunohistochemical (IHC) or fluorescent in situ hybridization analyses and CTCs were enumerated by CellSearch(®) at starting a new therapy. Overall survival (OS) and progression-free survival durations for each IHC subtype were determined.
  
  
  RESULTS
  At a median follow-up of 24.6 months, 276 of 517 (53%) patients had died. The median OS for patients with <5 and ≥ 5 CTCs were 32.4 and 18.3 months, respectively (P < 0.001). Except in HER2+ patients, the prognostic value of CTCs was independent of disease subtype and disease site.
  
  
  CONCLUSIONS
  In this large retrospective study, CTCs were strongly predictive of survival in all MBC subtypes except HER2+ patients who had been treated with targeted therapy. Our results clearly demonstrate the value of enumerating CTCs in MBC and strongly suggest an interesting biological implication in the HER2+ subset of patients that need to be further explored.
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, USA; Department of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Naples, Italy. Electronic address: agiordano@mdanderson.org.
authors.forename: A
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Naples, Italy; Department of Breast Cancer, Baylor College of Medicine, Houston, USA.
authors.forename: M
authors.initials: M
authors.lastname: Giuliano
authors.affiliation: Department of Breast Oncology, National Cancer Institute 'Fondazione Pascale', Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: De Laurentiis
authors.affiliation: Department of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Arpino
authors.affiliation: Departments of Breast Medical Oncology.
authors.forename: S
authors.initials: S
authors.lastname: Jackson
authors.affiliation: Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Handy
authors.affiliation: Departments of Breast Medical Oncology.
authors.forename: N T
authors.initials: NT
authors.lastname: Ueno
authors.affiliation: Departments of Breast Medical Oncology.
authors.forename: E
authors.initials: E
authors.lastname: Andreopoulou
authors.affiliation: Departments of Breast Medical Oncology.
authors.forename: R H
authors.initials: RH
authors.lastname: Alvarez
authors.affiliation: Departments of Breast Medical Oncology.
authors.forename: V
authors.initials: V
authors.lastname: Valero
authors.affiliation: Department of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: De Placido
authors.affiliation: Departments of Breast Medical Oncology.
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Reuben
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cristofanilli
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D002277:Carcinoma / Q000145:classification / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009367:Neoplasm Staging / Q000379:methods; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human