title: Serum HER2/ECD value in stage I and II early breast cancer: need of a lower cut-off?
abstract: BACKGROUND
  HER2 overexpression is well-established risk factor of worse prognosis in metastatic and early breast cancer. HER2 positivity can be determined from tumor tissue by immunohistochemical staining or by fluorescent in situ hybridization, or from serum by measuring concentration of HER2 receptor extracellular domain (HER2/ECD). HER2/ECD correlates well with worse prognosis in metastatic and locally advanced (stage III) disease if serum concentration is >15 ng/ml, but there are no consistent data for patients with early breast cancer.
  
  
  RESULTS
  41 patients with stage I and II breast cancer and 52 healthy controls were included into the study. HER2/ECD was determined before surgery and correlated with HER2/neu overexpression, Ki67, hormone receptor status and disease stage, and compared with value in healthy controls. Mean serum HER2/ECD concentration in patients was 8.62 ng/ml and 5.78 ng/ml in controls, and the difference was statistically significant (p = 0.000061). The best diagnostic cut-off value was 7.7 ng/ml, with 76.92% sensitivity and 72.92% specificity. Positive predictive value of the test was 69.77% and negative predictive value was 79.55%, with 74.71% of patients correctly classified. Serum HER2/ECD correlated with hormone receptors status, and no correlation with histological overexpression has been observed. CONCLUSION. Serum HER2/ECD concentration of ≥7.7 ng/ml has possible diagnostic value in stage I and II breast cancer. It should not be used as a determinant of HER2 positivity. Prognostic significance of HER2/ECD in early breast cancer, its correlation with hormone receptor status, and interconnection between hormone receptors and HER2 receptor signaling should be further analyzed, since it may have therapeutic implications.
authors: Department of Oncology, University Hospital Center Zagreb, Zagreb, Croatia. sbadzek@kbc-zagreb.hr
authors: Sasha
authors: S
authors: Badzek
authors: Vesna Lesko
authors: VL
authors: Kelovic
authors: Stjepko
authors: S
authors: Plestina
authors: Ines
authors: I
authors: Humar
authors: Zoran
authors: Z
authors: Veir
authors: Zeljko
authors: Z
authors: Mihaljevic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis*; D002352:Carrier Proteins / Q000097:blood*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human