title: Monitoring of serum Her-2/neu predicts response and progression-free survival to trastuzumab-based treatment in patients with metastatic breast cancer.
abstract: OBJECTIVE
  The present pilot study was performed to elucidate whether early changes in serum Her-2/neu extracellular domain (ECD) levels during trastuzumab-based treatment would predict the clinical course of disease in patients with metastatic breast cancer.
  
  
  METHODS
  Sera from 55 patients with Her-2/neu-overexpressing metastatic breast cancer obtained immediately before each weekly administration of trastuzumab were analyzed by a serum Her-2/neu ELISA.
  
  
  RESULTS
  Whereas response rates were significantly higher in patients with elevated (>or=15 ng/ml) ECD levels before initiation of treatment (35% versus 7%, P = 0.045), progression-free and overall survival did not differ significantly between patients with normal and elevated ECD levels. In patients responding to treatment, ECD levels decreased significantly as early as from day 8 of treatment onwards (all P for weekly measurements versus baseline <0.001). In contrast, no significant change in ECD levels was observed in patients with progressive disease. Multiple logistic regression analyses identified kinetics of ECD levels as the only factor that allowed for the accurate prediction of response likelihood as early as from day 8 of trastuzumab-based treatment onwards (P = 0.020). In addition, determination of serial ECD levels allowed for the prediction of the risk for disease progression within the observed period as early as day 15 of treatment (P = 0.010).
  
  
  CONCLUSIONS
  Serial monitoring of the ECD may represent a valuable tool for early prediction of the probability of response and progression-free survival to trastuzumab-based treatment and is thus likely to contribute to an optimization of treatment and resource allocation.
authors.affiliation: Department of Medicine I, University Hospital of Vienna, Austria. wolfgamg.koestler@akh-wien.ac.at
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Köstler
authors.forename: Barbara
authors.initials: B
authors.lastname: Schwab
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Rainer
authors.initials: R
authors.lastname: Neumann
authors.forename: Ernst
authors.initials: E
authors.lastname: Rücklinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodowicz
authors.forename: Sandra
authors.initials: S
authors.lastname: Tomek
authors.forename: Monika
authors.initials: M
authors.lastname: Niedermayr
authors.forename: Michael
authors.initials: M
authors.lastname: Hejna
authors.forename: Günther G
authors.initials: GG
authors.lastname: Steger
authors.forename: Michael
authors.initials: M
authors.lastname: Krainer
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiltschke
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000188:drug therapy / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004784:Environmental Monitoring / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011336:Probability; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D013997:Time Factors; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab