title: High concordance of protein (by IHC), gene (by FISH; HER2 only), and microarray readout (by TargetPrint) of ER, PgR, and HER2: results from the EORTC 10041/BIG 03-04 MINDACT trial.
abstract: BACKGROUND
  To investigate the correlation of TargetPrint with local and central immunohistochemistry/fluorescence in situ hybridization assessment of estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) in the first 800 patients enrolled in the MINDACT trial.
  
  
  METHODS
  Data from local (N = 800) and central (N = 626) assessments of receptor status were collected and compared with TargetPrint results.
  
  
  RESULTS
  For ER, the positive agreement (the percentage of central pathology positive assessments that were also TargetPrint/local laboratory positive) for TargetPrint in comparison to centralized assessment was 98% with a negative agreement (the percentage of central pathology negative assessments that were also TargetPrint/local laboratory negative) of 96%. For PgR, the positive agreement was 83% with a negative agreement of 92%. For HER2, the positive agreement was 75% with a negative agreement of 99%. Even though the local assessment showed higher positive agreement for PgR (89%) and higher positive agreement for HER2 (85%), the range of discordant local versus central assessments were as high as 6.7% for ER, 12.9% for PgR, and 4.3% for HER2.
  
  
  CONCLUSIONS
  TargetPrint and local assessment of ER, PgR, and HER2 show high concordance with central assessment in the first 800 MINDACT patients. However, there are concerns about the higher discordance rates for some local sites. TargetPrint can improve the reliability of hormone receptor and HER2 testing for those centers with a lower rate of concordance with the reference laboratory, with the limitation of a positive agreement of 75% for HER2. TargetPrint consequently has important implications for treatment decisions in clinical practice and is a reliable alternative to local assessment for ER.
  
  
  BACKGROUND
  NCT00433589.
authors.affiliation: Department of Pathology, European Institute of Oncology and University of Milan, Milan, Italy. Electronic address: giuseppe.viale@ieo.it.
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.affiliation: Department of Statistics, European Organization for Research and Treatment of Cancer, Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Slaets
authors.affiliation: Department of Statistics, European Organization for Research and Treatment of Cancer, Brussels, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Bogaerts
authors.affiliation: Department of Surgery, Netherlands Cancer Institute, Amsterdam.
authors.forename: E
authors.initials: E
authors.lastname: Rutgers
authors.affiliation: Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA; Research and Development, Agendia, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Van't Veer
authors.affiliation: Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: M J
authors.initials: MJ
authors.lastname: Piccart-Gebhart
authors.affiliation: Medical Affairs, Agendia, Amsterdam, The Netherlands.
authors.forename: F A
authors.initials: FA
authors.lastname: de Snoo
authors.affiliation: Medical Affairs, Agendia, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Stork-Sloots
authors.affiliation: Department of Pathology, European Institute of Oncology and University of Milan, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Russo
authors.affiliation: Department of Pathology, European Institute of Oncology and University of Milan, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Dell'Orto
authors.affiliation: Research and Development, Agendia, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van den Akker
authors.affiliation: Research and Development, Agendia, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Glas
authors.affiliation: Breast Unit, Champalimaud Cancer Center, Lisbon, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Cardoso
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D046228:Microarray Analysis; D008875:Middle Aged; D011379:Prognosis; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D013223:Statistics as Topic
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: FISH; IHC; TargetPrint; breast cancer; concordance; hormone receptor