title: Serum HER-2 predicts response and resistance to trastuzumab treatment in breast cancer.
abstract: BACKGROUND
  Serum HER2 (S-HER2) was approved in 2003 by the US Food and Drug Administration (FDA) for monitoring trastuzumab treatment in tissue HER2 positive breast cancer patients. Information of the value of S-HER2 is scarce. We hypothesised that S-HER2 would reflect the clinical effect of trastuzumab.
  
  
  METHODS
  We followed 48 patients eligible for trastuzumab treatment for up to 6 years or until death. S-HER2 was measured on an ADVIA Centaur System and S-Trastuzumab was measured by an in-house developed fluorescent enzyme immunoassay system on the ImmunoCap 100.
  
  
  RESULTS
  A decrease in S-HER2 of ≥ 20% was correlated to no progression in the disease in 20 out of 21 clinical courses (p<0.0001). An increase in S-HER2 of ≥ 20% was correlated to progression in the disease in 40 out of 44 clinical courses (p<0.0001). Patients with no recurrence after trastuzumab treatment (n=18) had a median S-HER2 concentration of 10.5 μg/L, whereas patients alive with recurrence (n=13) had a median S-HER2 of 20.1 μg/L (p=0.002). Patients who died prompted by recurrence (n=17) had a median S-HER2 of 232.4 μg/L at latest measurement before death (p=<0.0001) compared to patients without recurrence. In two patients with S-HER2 values above 1000 μg/L the concentrations of S-trastuzumab were measured below the target trough concentration in serum of 10 mg/L.
  
  
  CONCLUSIONS
  Decreasing values of S-HER2 predicts response to treatment whereas increasing levels predict resistance. S-HER2 above 1000 μg/L warns that standard doses of trastuzumab may be insufficient as reflected by low concentrations of S-trastuzumab.
authors: Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Kabbeltoft 25, 7100 Vejle, Denmark. eva.rabing.brix.petersen@slb.regionsyddanmark.dk
authors: Eva Rabing Brix
authors: ER
authors: Petersen
authors: Patricia Diana
authors: PD
authors: Sørensen
authors: Erik Hugger
authors: EH
authors: Jakobsen
authors: Jonna Skov
authors: JS
authors: Madsen
authors: Ivan
authors: I
authors: Brandslund
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D002278:Carcinoma in Situ / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human