title: Biomarkers characterization of circulating tumour cells in breast cancer patients.
abstract: BACKGROUND
  Increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcomes of nonmetastatic breast cancer patients. CTCs differ genetically from the primary tumor and may contribute to variations in prognosis and response to therapy. As we start to understand more about the biology of CTCs, we can begin to address how best to treat this form of disease.
  
  
  METHODS
  Ninety-eight nonmetastatic breast cancer patients were included in this study. CTCs were isolated by immunomagnetic techniques using magnetic beads labelled with a multi-CK-specific antibody (CK3-11D5) and CTC detection through immunocytochemical methods. Estrogen receptor, progesterone receptor and epidermal growth factor receptor (EGFR) were evaluated by immunofluorescence experiments and HER2 and TOP2A by fluorescence in situ hybridization. We aimed to characterize this set of biomarkers in CTCs and correlate it with clinical-pathological characteristics.
  
  
  RESULTS
  Baseline detection rate was 46.9% ≥ 1 CTC/30 ml threshold. CTC-positive cells were more frequent in HER2-negative tumors (p = 0.046). In patients younger than 50 years old, HER2-amplified and G1-G2 tumors had a higher possibility of being nondetectable CTCs. Heterogeneous expression of hormonal receptors (HRs) in samples from the same patients was found. Discordances between HR expression, HER2 and TOP2A status in CTCs and their primary tumor were found in the sequential blood samples. Less that 35% of patients switched their CTC status after receiving chemotherapy. EGFR-positive CTCs were associated with Luminal tumors (p = 0.03).
  
  
  CONCLUSIONS
  This is the largest exploratory CTC biomarker analysis in nonmetastatic BC patients. Our study suggests that CTC biomarkers profiles might be useful as a surrogate marker for therapeutic selection and monitoring since heterogeneity of the biomarker distribution in CTCs and the lack of correlation with the primary tumor biomarker status were found. Further exploration of the association between EGFR-positive CTCs and Luminal tumors is warranted.
authors.affiliation: Pfizer-University of Granada-Andalusian Government Center of Genomics and Oncology (GENyO), Avenida de la Ilustración, 114, Granada, ES-18007, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Nadal
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez
authors.forename: Pedro
authors.initials: P
authors.lastname: Sanchez-Rovira
authors.forename: Marta
authors.initials: M
authors.lastname: Salido
authors.forename: María
authors.initials: M
authors.lastname: Rodríguez
authors.forename: José Luis
authors.initials: JL
authors.lastname: García-Puche
authors.forename: Marta
authors.initials: M
authors.lastname: Macià
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Corominas
authors.forename: Miguel
authors.initials: M
authors.lastname: Delgado-Rodriguez
authors.forename: Lucas
authors.initials: L
authors.lastname: Gonzalez
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.forename: Mónica
authors.initials: M
authors.lastname: Fernández
authors.forename: Francesc
authors.initials: F
authors.lastname: Solé
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Lorente
authors.forename: María José
authors.initials: MJ
authors.lastname: Serrano
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D007633:Keratins; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human; C000618811:TOP2A protein, human