title: Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial.
abstract: BACKGROUND
  Perioperative epirubicin, cisplatin and fluorouracil (ECF) chemotherapy improves survival in operable oesophago-gastric cancer [Adjuvant Gastric Cancer Infusional Chemotherapy (MAGIC) trial HR 0.75 (0.6-0.93)]. HER2 amplification is reported to predict enhanced benefit from anthracyclines in breast cancer. We sought to define whether HER2 predicts benefit from ECF in oesophago-gastric cancer.
  
  
  METHODS
  Diagnostic biopsies and/or resection specimens were collected from 415 of 503 MAGIC trial patients (82.5%). HER2 was evaluated by immunohistochemistry (IHC) and brightfield dual in situ hybridisation (BDISH) in tissue microarrays. The prognostic and predictive impact of HER2 status was investigated.
  
  
  RESULTS
  Concordance between HER2 over-expression (IHC3+) and amplification was 96%. Results of HER2 assessment in biopsy and resection specimens were concordant in 92.9% (145/156). HER2 positive rate (IHC3+, or IHC2+/BDISH positive) was 10.9% in the whole cohort and 10.4% in resection specimens. A further 4.0% of resections were IHC negative/BDISH positive. HER2 status was neither prognostic, nor (in pre-treatment biopsies) predicted enhanced benefit from chemotherapy [HER2 positive HR 0.74 (0.14-3.77); HER2 negative HR 0.58 (0.41-0.82), interaction P = 0.7]. However, the power of the predictive analysis was limited by the small number of HER2 positive pre-treatment biopsies.
  
  
  CONCLUSIONS
  HER2 status is not an independent prognostic biomarker in early oesophago-gastric adenocarcinoma.
authors.affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey.
authors.forename: A F C
authors.initials: AF
authors.lastname: Okines
authors.forename: L C
authors.initials: LC
authors.lastname: Thompson
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: A
authors.initials: A
authors.lastname: Wotherspoon
authors.forename: J S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: R E
authors.initials: RE
authors.lastname: Langley
authors.forename: T S
authors.initials: TS
authors.lastname: Waddell
authors.forename: D
authors.initials: D
authors.lastname: Noor
authors.forename: Z
authors.initials: Z
authors.lastname: Eltahir
authors.forename: R
authors.initials: R
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: Stenning
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D015251:Epirubicin / Q000627:therapeutic use; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D059035:Perioperative Period; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002945:Cisplatin; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human