title: Highly reproducible results of breast cancer biomarkers when analysed in accordance with national guidelines - a Swedish survey with central re-assessment.
abstract: BACKGROUND
  Biomarkers are crucial for decisions regarding adjuvant therapy in primary breast cancer, and their correct assessment is therefore of the utmost importance.
  
  
  OBJECTIVE
  To investigate the concordance between Swedish pathology departments and a reference laboratory, for routine analysis of oestrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2), alone, and in combination (St Gallen subtypes).
  
  
  METHODS
  This survey included 27 of the 28 pathology laboratories in Sweden, covering 98% of cases of primary breast cancer surgery in Sweden. Paraffin-embedded tumour blocks (n = 270) were collected and sent to the central reference laboratory, together with the originally stained slides, for re-analysis. The primary evaluations were previously performed according to national Swedish guidelines, without any knowledge of the subsequent central assessment.
  
  
  RESULTS
  The agreement for ER, PR, and Ki67 was 99% [kappa value (κ) = 0.95], 95% (κ = 0.85), and 85% (κ = 0.70), respectively. The agreement for HER2 (0/1 + vs. 2+/3+) was 85% (κ = 0.64), but when equivocal tumours were further analysed with in situ hybridisation, only one discrepancy was observed. Discrepancies between results for ER and PR seem to be explained by analytical differences, whereas the interpretation of staining seems to be more critical for Ki67 and HER2 immunohistochemistry. The agreement between the results from the Swedish laboratories and the reference laboratory, based on the St Gallen subtypes, was 88% (κ = 0.81).
  
  
  CONCLUSIONS
  When applying national guidelines, highly reproducible results were obtained in routine assessment of breast cancer biomarkers, and the results of this study confirm the clinical utility of these markers for decisions regarding the treatment of primary breast cancer.
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University , Lund , Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Ekholm
authors.forename: Dorthe
authors.initials: D
authors.lastname: Grabau
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Göran
authors.initials: G
authors.lastname: Elmberger
authors.forename: Hans
authors.initials: H
authors.lastname: Olsson
authors.forename: Leila
authors.initials: L
authors.lastname: Russo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards*; D019394:Ki-67 Antigen / Q000032:analysis; D017410:Practice Guidelines as Topic; D011785:Quality Assurance, Health Care; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D015203:Reproducibility of Results; D011795:Surveys and Questionnaires; D013548:Sweden
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human