Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial

A. F.C. Okines, L. C. Thompson, D. Cunningham, A. Wotherspoon, J. S. Reis-filho, R. E. Langley, T. S. Waddell, D. Noor, Z. Eltahir, R. Wong, S. Stenning

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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. Patients and 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.

Original languageEnglish
Article numbermds622
Pages (from-to)1253-1261
Number of pages9
JournalAnnals of Oncology
Volume24
Issue number5
DOIs
Publication statusPublished - 1 May 2013

Keywords

  • Adenocarcinoma
  • Gastric
  • HER2
  • Immunohistochemistry
  • In situ hybridisation
  • Oesophageal

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