title: Serum IGF-1, IGFBP-3 levels and circulating tumor cells (CTCs) in early breast cancer patients.
abstract: Insulin-like growth factor (IGF)-axis is involved in human oncogenesis and metastasis development for various solid tumors including breast cancer. Aim of this study was to assess the association between IGF-1, IGF-binding protein-3 (IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the peripheral blood of women diagnosed with early breast cancer (EBC), before and after adjuvant chemotherapy.
  
  
  
  171 patients with early-stage breast adenocarcinomas were retrospectively evaluated. Immunoradiometric (IRMA) assays were employed for the in-vitro determination of IGF-1 and IGFBP-3 serum levels in blood samples collected after surgical treatment and before initiation of adjuvant chemotherapy. CTCs' presence was assessed through detection of cytokeratin-19 (CK-19) mRNA transcripts using quantitative real time reverse transcription polymerase chain reaction (RT-PCR). IGF-1, IGFBP-3 serum levels were correlated with CTCs' presence before and after adjuvant chemotherapy as well as with tumor characteristics including tumor size, axillary lymph node status, oestrogen (ER)/progestorene (PR) and human epidermural growth factor receptor 2 (HER2) receptor status. Log-rank test was applied to investigate possible association between IGF-1, IGFBP-3 serum levels and disease-free interval (DFI) and overall survival (OS).
  
  
  
  Before initiation of adjuvant therapy IGF-1, IGFBP-3 serum levels were moderately associated (Spearman's rho=0.361, p<0.001) with each other, while presenting significant differences across age groups (all p values<0.05). IGF-1 serum levels did not correlate with the presence of CTCs before initiation (p=0.558) or after completion (p=0.474) of adjuvant chemotherapy. Similarly, IGFBP-3 serum levels did not show significant association with detectable CTCs either before (p=0.487) or after (p=0.134) completion of adjuvant chemotherapy. There was no statistically significant association between the clinical outcome of patients in terms of DFI, OS and IGF-1(DFI: p=0.499; OS: p=0.220) or IGFBP-3 (DFI: p=0.900; OS: p=0.406) serum levels.
  
  
  
  IGF-1 and IGFBP-3 serum levels before initiation of adjuvant chemotherapy are not indicative of CTCs' presence in the blood and do not correlate with clinical outcome of women with early-stage breast cancer.
authors.affiliation: Faculty of Medicine, University of Crete, Greece; Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center (CC), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address: papadakisg@cc.nih.gov.
authors.forename: Georgios Z
authors.initials: GZ
authors.lastname: Papadakis
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, School of Medicine, University of Crete, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mavroudis
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, School of Medicine, University of Crete, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Georgoulias
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, School of Medicine, University of Crete, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Souglakos
authors.affiliation: Center of Toxicology Science & Research, Division of Morphology, Medical School, University of Crete, Heraklion, Crete, Greece.
authors.forename: Athanasios K
authors.initials: AK
authors.lastname: Alegakis
authors.affiliation: Department of Internal Medicine, University of Crete, Heraklion, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Samonis
authors.affiliation: Center for Research in Computer Vision (CRCV), Electrical and Computer Science Department, University of Central Florida (UCF), Orlando, FL 32816, USA.
authors.forename: Ulas
authors.initials: U
authors.lastname: Bagci
authors.affiliation: Department of Obstetrics and Gynecology, Medical School, University of Crete, Heraklion, Greece.
authors.forename: Antonis
authors.initials: A
authors.lastname: Makrigiannakis
authors.affiliation: Department of Surgical Oncology, University Hospital of Heraklion, Crete, Greece.
authors.forename: Odysseas
authors.initials: O
authors.lastname: Zoras
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: C583557:IGF1 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I
keywords: Biomarkers; Circulating tumor cells (CTCs); Early breast cancer (EBC); IGF-binding protein-3 (IGFBP-3); Insulin-like growth factor-1 (IGF-1); Prognosis