title: Predicting tissue HER2 status using serum HER2 levels in patients with metastatic breast cancer.
abstract: BACKGROUND
  Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) are reliable ways to identify overexpression or amplification of the HER-2/neu (HER2, symbol ERBB2) gene, but each technique requires a high-quality tissue sample, which may not be available. We investigated whether serum concentrations of the HER2 extracellular domain (ECD) can be used as an alternative to tissue HER2 status in metastatic breast cancer, and we defined an optimal decision-level concentration of serum HER2 for prediction of tissue HER2 status.
  
  
  METHODS
  In 195 patients with metastatic breast cancer, we determined HER2 expression by IHC and performed FISH analysis on tumors for which IHC staining was graded as 2+. We measured serum HER2 by immunoassay and used ROC curve analysis to determine optimal serum HER2 ECD concentrations for differentiation between positive and negative HER2 status.
  
  
  RESULTS
  IHC results were 0/1+ for 30 (15%) of the patients, 2+ for 89 (46%), and 3+ for 76 (39%). FISH revealed HER2 amplification in 19 (21%) of the IHC 2+ tumors. Mean (SE) serum HER2 ECD was 22.2 (5.1) microg/L in the tissue HER2-negative group, significantly lower than the concentration of 363 (96) microg/L in the tissue HER2-positive group (P<0.0001). ROC curve analysis showed 95% specificity and 62% sensitivity for tissue HER2 positivity at 37 microg/L of serum HER2.
  
  
  CONCLUSIONS
  To use serum HER2 concentration as an alternative to direct determination of tissue HER2 status, we suggest 37 microg/L as a cutoff for predicting positive tissue HER2 with 95% specificity. Sensitivity, however, is low.
authors.affiliation: Research Institute & Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kong
authors.forename: Byung-Ho
authors.initials: BH
authors.lastname: Nam
authors.forename: Keun Seok
authors.initials: KS
authors.lastname: Lee
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Kwon
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.forename: Do Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Jungsil
authors.initials: J
authors.lastname: Ro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases