title: Changes over time of extracellular domain of HER2 (ECD/HER2) serum levels have prognostic value in metastatic breast cancer.
abstract: BACKGROUND
  Blood levels of the extracellular domain of HER-2/neu (ECD/HER2) have been suggested to have potential as a tumor marker in breast cancer. Our aim was to assess the prognostic value of baseline levels of ECD/HER2, but more importantly changes in levels over time, in women with metastatic breast cancer.
  
  
  METHODS
  Baseline and serial levels of ECD/HER2 were measured in 158 women with newly-diagnosed metastatic breast cancer, in whom we previously performed serial measurement of plasma osteopontin. ECD/HER2 was measured in 1,282 serum samples using a validated ELISA at baseline and every 3-12 weeks during and after therapy until death (median, n=8 samples per patient). Multivariate time-dependent survival analyses were conducted using models that right-censored patient outcomes 3, 6 and 12 months after last known ECD/HER2 measurement.
  
  
  RESULTS
  Thirty-four patients (22%) had elevated baseline ECD/HER2 (median 10.2 ng/ml: range 4.1-40.4 ng/ml). In univariate analysis, elevated baseline ECD/HER2 was associated with short survival (P=0.001). In a multivariate model incorporating standard clinical prognostic factors, baseline ECD/HER2 was significantly associated with survival duration (RR 1.029; P=0.020). Presence of visceral metastases and ECOG status 2-4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential ECD/HER2 levels, an ECD/HER2 increase of >12 ng/ml at any time was the variable with most prognostic value for poor survival (RR 6.10; P=0.0003); poor ECOG status also retained significance.
  
  
  CONCLUSIONS
  Increases over time of ECD/HER2 levels were strongly associated with poor survival in this cohort of women with metastatic breast cancer.
authors.affiliation: London Regional Cancer Program, London, ON, Canada. vivienbr@cancerboard.ab.ca
authors.forename: Vivien H C
authors.initials: VH
authors.lastname: Bramwell
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Doig
authors.forename: Alan B
authors.initials: AB
authors.lastname: Tuck
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Wilson
authors.forename: Katia S
authors.initials: KS
authors.lastname: Tonkin
authors.forename: Anna
authors.initials: A
authors.lastname: Tomiak
authors.forename: Francisco
authors.initials: F
authors.lastname: Perera
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Vandenberg
authors.forename: Ann F
authors.initials: AF
authors.lastname: Chambers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000737:chemistry; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000401:mortality*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000737:chemistry; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases