title: Serum HER-2: sensitivity, specificity, and predictive values for detecting metastatic recurrence in breast cancer patients.
abstract: OBJECTIVE
  The aim of this study was to determine the sensitivity, specificity, and predictive values of serum HER-2 for detecting metastatic recurrence in breast cancer patients.
  
  
  METHODS
  In the period 2004-2009, serum HER-2 was measured in 1,348 patients with breast cancer: 837 during routine controls at the Oncology Department and 511 newly diagnosed. The patients with positive serum HER-2, all the newly diagnosed and 1/5 of the patients with negative serum HER-2 were followed with serum HER-2 measurements every 3-12 months using the ADVIA Centaur assay. Tissue HER-2 status was determined by IHC and FISH. Patients with a single serum HER-2 value above 15 μg/L were considered serum positive. Metastases were diagnosed according to the routine clinical methods using imaging/biopsy.
  
  
  RESULTS
  Of the 862 patients included, 21 had unavailable medical records and were excluded. Patients with unknown tissue status (218), missing blood sample before recurrence (74), or presenting with primary metastatic disease (9) were also excluded. Blood samples before the detection of metastatic recurrence were available in 154 tissue HER-2-positive and in 386 tissue HER-2-negative patients. The sensitivity, specificity, positive and negative predictive values in tissue HER-2-positive patients with values above 15 μg/L were 69 % (95 % CI 53-80 %), 71 % (62-78), 47 % (35-59), and 86 % (77-91), respectively. Combining the cutoff value of 15 μg/L with a delta value of >100 % increase from individual baseline after primary therapy, or increasing the cutoff to 32 μg/L raises the specificity to 96 %, but lowers the sensitivity to 50 and 47 %, respectively. Preoperative serum HER-2 values were accessible in 69 tissue-positive patients, but no significant association was found with later development of metastases. The sensitivity, specificity, positive and negative predictive values in tissue HER-2-negative patients with values above 15 μg/L were 33 % (21-47), 77 % (73-82), 18 % (12-27), and 88 % (84-91), respectively.
  
  
  CONCLUSIONS
  Monitoring tissue HER-2-positive breast cancer patients with serum HER-2 has a sufficient sensitivity to detect metastatic recurrence, while its use in monitoring of tissue HER-2-negative patients is unsatisfactory.
authors.affiliation: Department of Clinical Biochemistry, Lillebaelt Hospital, Kabbeltoft 25, 7100, 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: Jonna Skov
authors.initials: JS
authors.lastname: Madsen
authors.forename: Eva Brix
authors.initials: EB
authors.lastname: Petersen
authors.forename: Rikke Fredslund
authors.initials: RF
authors.lastname: Andersen
authors.forename: Birthe
authors.initials: B
authors.lastname: Østergaard
authors.forename: Ivan
authors.initials: I
authors.lastname: Brandslund
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases