title: Discrepancies in central review re-testing of patients with ER-positive and HER2-negative breast cancer in the OPTIMA prelim randomised clinical trial.
abstract: BACKGROUND
  There is limited data on results of central re-testing of samples from patients with invasive breast cancer categorised in their local hospital laboratories as oestrogen receptor (ER) positive and human epidermal growth factor receptor homologue 2 (HER2) negative.
  
  
  METHODS
  The Optimal Personalised Treatment of early breast cancer usIng Multiparameter Analysis preliminary study (OPTIMA prelim) was the feasibility phase of a randomised controlled trial to validate the use of multiparameter assay-directed chemotherapy decisions in the UK National Health Service (NHS). Eligibility criteria included ER positivity and HER2 negativity. Central re-testing of receptor status was mandatory.
  
  
  RESULTS
  Of the 431 patients tested centrally, discrepant results between central and local laboratory results were identified in only 19 (4.4%; 95% confidence interval 2.5-6.3%) patients (with 21 tumours). On central review, seven patients had cancers that were ER-negative (1.6%) and 13 (3.0%) patients with 15 tumours had HER2-positive disease, including one tumour discrepant for both biomarkers.
  
  
  CONCLUSIONS
  Central re-testing of receptor status of invasive breast cancers in the UK NHS setting shows a high level of reproducibility in categorising tumours as ER-positive and HER2-negative, and raises questions regarding the cost effectiveness and clinical value of central re-testing in this sub-group of breast cancers in this setting.
authors.affiliation: Division of Cancer Studies, King's College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: Pinder
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Gibbet Hill Campus, Coventry CV4 7AL, UK.
authors.forename: A F
authors.initials: AF
authors.lastname: Campbell
authors.affiliation: Ontario Institute of Cancer Research, Toronto, Ontario M5G 0A3, Canada.
authors.forename: J M S
authors.initials: JM
authors.lastname: Bartlett
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Gibbet Hill Campus, Coventry CV4 7AL, UK.
authors.forename: A
authors.initials: A
authors.lastname: Marshall
authors.affiliation: UCL-Advanced Diagnostics, University College London, 21 University Street, London WC1E 6JJ, UK.
authors.forename: D
authors.initials: D
authors.lastname: Allen
authors.affiliation: Department of Pathology, University College London Hospitals, 235, Euston Road, London NW1 2BU, UK.
authors.forename: M
authors.initials: M
authors.lastname: Falzon
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Gibbet Hill Campus, Coventry CV4 7AL, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Dunn
authors.affiliation: Department of Clinical Oncology, Mount Vernon Cancer Centre, Mount Vernon Hospital, Northwood, HA6 2RN, UK.
authors.forename: A
authors.initials: A
authors.lastname: Makris
authors.affiliation: Oncology Centre, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: L
authors.initials: L
authors.lastname: Hughes-Davies
authors.affiliation: Department of Oncology, University College London Hospitals, London NW1 2PG, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Stein
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D020000:Decision Support Systems, Clinical / Q000592:standards*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D013677:Medical Laboratory Science / Q000379:methods*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D015203:Reproducibility of Results; D012107:Research Design
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human