title: Serum HER-2 concentrations for monitoring women with breast cancer in a routine oncology setting.
abstract: BACKGROUND
  The purpose of this study was to determine the positive predictive value (PPV) of positive serum human epidermal growth factor receptor-2 (HER-2) for monitoring women with breast cancer following diagnosis and treatment in a routine clinical setting.
  
  
  METHODS
  Serum HER-2 was measured in 1348 patients with breast cancer: 837 during routine oncology clinic visits and 511 following new diagnosis. All patients with positive serum HER-2, 1/5 of negative patients from the oncology clinic, and all the newly diagnosed were followed; a total of 862 patients. Serum HER-2 was measured using the Bayer ADVIA Centaur assay. Tissue HER-2 was determined using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). IHC +3 or IHC +2 and FISH>2.0 were positive. Patients were considered to have positive serum HER-2 when at least two values were >15 ng/mL. Recurrence, progression and regression were diagnosed according to usual clinical practice. Serum HER-2 concentrations did not contribute to diagnostic decision-making or selection of treatment.
  
  
  RESULTS
  From January 2004 to January 2009, 149 patients were found to have positive serum HER-2. Of these, 35 were tissue HER-2 positive at surgery, 69 tissue-negative and 45 were not determined. Fifty-five of 149 that were serum HER-2 positive (37%, 95% CI: 29-45) had metastases. Among the 35 tissue-positive patients, 25 had recurrence in the form of metastases and there was good correlation between recurrence/progression and increase in serum HER-2 (p<0.0003). There was also a high correlation between effect of treatment and decline in serum HER-2 (p<0.0003). Of the 69 tissue-negative patients, 29 had recurrence in the form of metastases, and there was good correlation with serum HER-2 levels (p<0.000004). In this routine application of serum HER-2, the PPV for metastases recurrence detection in both tissue-positive and tissue-negative was 54 of 104 (52%, 95% CI: 42%-62%), in tissue-positive 25 of 35 (71%, 95% CI: 54%-85%), in tissue-negative 29 of 69 (42%, 95% CI: 30%-54%). The lead time of increases in serum HER-2 before recurrence could be determined in ten tissue-positive patients was 3-24 months (mean 11.3 months), when compared to standard clinical imaging methods.
  
  
  CONCLUSIONS
  Serum HER-2 is a useful marker for the detection of recurrence of breast cancer and for monitoring the effect of treatment, especially in tissue HER-2 positive patients.
authors.affiliation: Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark. Patricia.Diana.Soerensen@slb.regionsyddanmark.dk
authors.forename: Patricia Diana
authors.initials: PD
authors.lastname: Sørensen
authors.forename: Erik Hugger
authors.initials: EH
authors.lastname: Jakobsen
authors.forename: Sven Tyge
authors.initials: ST
authors.lastname: Langkjer
authors.forename: Susanne
authors.initials: S
authors.lastname: Bokmand
authors.forename: Birthe
authors.initials: B
authors.lastname: Østergaard
authors.forename: Dorte Aalund
authors.initials: DA
authors.lastname: Olsen
authors.forename: Jonna Skov
authors.initials: JS
authors.lastname: Madsen
authors.forename: Ivan
authors.initials: I
authors.lastname: Brandslund
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human