title: Preoperative serum HER2 extracellular domain levels in primary invasive breast cancer.
abstract: BACKGROUND
  Despite the preclinical outcomes and biologic significance of the presence of the human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD), there is little evidence supporting the measurement of ECD levels in any clinical setting. The aim of this study was to determine the prevalence of elevated serum HER2 ECD levels, the association between these levels and tissue HER2 overexpression, and the potential clinical prognostic value of HER2 ECD in primary invasive breast cancer.
  
  
  METHODS
  Serum HER2 ECD levels were examined preoperatively in 2,862 consecutive stage I-III primary breast cancer patients between 2007 and 2009. Serum HER2 ECD levels were measured by chemiluminescence immunoassay (ADVIA Centaur), and the tissue HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. The cutoff value for the serum level of HER2 ECD was set at 15.2 ng/ml.
  
  
  RESULTS
  Among the 2,862 patients, 126 (4.4%) had elevated serum HER2 ECD levels, and HER2 was overexpressed in the tumor tissue of 692 patients (24.2%), with a concordance of 78.7%. Multivariate analysis revealed that elevated serum HER2 ECD was a significant independent prognostic factor for worse distant-metastasis-free survival [DMFS; hazard ratio (HR) = 2.50, 95% confidence interval (CI) = 1.5-4.3, P = 0.001] and breast-cancer-specific survival (BCSS; HR = 2.0, 95% CI = 1.1-3.8, P = 0.036), which were much stronger in patients with tissue HER2-positive tumors (DMFS: HR = 3.8, 95% CI = 2.0-7.0, P < 0.001; BCSS: HR = 2.6, 95% CI = 1.2-5.3, P = 0.012).
  
  
  CONCLUSIONS
  Given the prevalence of HER2 expression, its measurement as an independent prognostic factor can be clinically useful, particularly in patients with tissue HER2-positive tumors.
authors.forename: Sae Byul
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap 2 dong, Songpa-Gu, Seoul 138-736, Korea. jongwonlee116@gmail.com.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Yu
authors.forename: Beom Seok
authors.initials: BS
authors.lastname: Ko
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Son
authors.forename: Gyungyub
authors.initials: G
authors.lastname: Gong
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung-Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Kyung Hae
authors.initials: KH
authors.lastname: Jung
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Woochang
authors.initials: W
authors.lastname: Lee
authors.forename: Joohon
authors.initials: J
authors.lastname: Sung
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D057234:Preoperative Period; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000235:genetics; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human