title: Impact of HER2 copy number in IHC2+/FISH-amplified breast cancer on outcome of adjuvant trastuzumab treatment in a large UK cancer network.
abstract: BACKGROUND
  Adjuvant trastuzumab with chemotherapy is standard treatment for HER2-positive breast cancer, defined as either HER2 IHC3+ or IHC2+ and FISH amplified. The aim of this study was to investigate the degree to which HER2 amplification in terms of HER2 gene copy numbers in HER2+IHC2+ cancers affected the outcome in a community setting.
  
  
  METHODS
  Case records of 311 consecutive patients with early breast cancer presenting between 1st January 2005 and 31st December 2008 were reviewed. Progression-free survival and overall survival were calculated with the Kaplan-Meier method using STATA 13.
  
  
  RESULTS
  Among 3+ cases (n=230) 163 received T vs 67 no-T. Among 2+ cases (n=81) 59 received T vs 22 no-T. Among 59 IHC2+-treated cases n=28 had an average of >12, n=13 had >6 to <12, and n=18 had >2 to <6 HER2 gene copies, respectively. The time of progression and overall survival of high and low copy number patients was similar and better than the intermediate copy number and the untreated cohorts.
  
  
  CONCLUSIONS
  High HER2 copy number (>12) appears to be associated with consistently better response compared with patients with intermediate HER2 copy numbers (6-12). In light of emerging data of patients showing insensivity to trastuzumab therapy, we propose that the HER2 gene copy number value should be included as an additional indicator for stratifying both the management and the follow-up of breast cancer patients.
authors.affiliation: Velindre Cancer Centre, Whitchurch, Cardiff CF14 2TL, UK.
authors.forename: A
authors.initials: A
authors.lastname: Borley
authors.affiliation: Cardiff University School of Medicine, Heath Park, Cardiff CF14 4YU, UK.
authors.forename: T
authors.initials: T
authors.lastname: Mercer
authors.affiliation: Department of Cellular Pathology, University Hospital of Wales, Heath Park, Cardiff CF14 4YU, UK.
authors.forename: M
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Wales Cancer Trials Unit, Neuadd Meirionnydd, Heath Park, Cardiff CF14 4YS, UK.
authors.forename: P
authors.initials: P
authors.lastname: Dutton
authors.affiliation: Velindre Cancer Centre, Whitchurch, Cardiff CF14 2TL, UK.
authors.forename: P
authors.initials: P
authors.lastname: Barrett-Lee
authors.affiliation: Department of Pathology and Diagnostic, University of Verona, Verona 37134, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Institute of Cancer & Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: B
authors.initials: B
authors.lastname: Jasani
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human