title: Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial.
abstract: BACKGROUND
  Trastuzumab has been approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric carcinoma; however, relatively little is known about the role of HER2 in the natural history of this disease.
  
  
  METHODS
  Patients enrolled in the INT-0116/SWOG9008 phase III gastric cancer clinical trial with available tissue specimens were retrospectively evaluated for HER2 gene amplification by FISH and overexpression by immunohistochemistry (IHC). The original trial was designed to evaluate the benefit of postoperative chemoradiation compared with surgery alone.
  
  
  RESULTS
  HER2 gene amplification rate by FISH was 10.9% among 258 patients evaluated. HER2 overexpression rate by IHC was 12.2% among 148 patients evaluated, with 90% agreement between FISH and IHC. There was a significant interaction between HER2 amplification and treatment with respect to both disease-free survival (DFS) (P = 0.020) and overall survival (OS) (P = 0.034). Among patients with HER2-non-amplified cancers, treated patients had a median OS of 44 months compared with 24 months in the surgery-only arm (P = 0.003). Among patients with HER2-amplified cancers, there was no significant difference in survival based on treatment arm. HER2 status was not a prognostic marker among patients who received no postoperative chemoradiation.
  
  
  CONCLUSIONS
  Patients lacking HER2 amplification benefited from treatment as indicated by both DFS and OS.
  
  
  BACKGROUND
  INT-0116/SWOG9008 phase III.
authors.affiliation: Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles.
authors.forename: M A
authors.initials: MA
authors.lastname: Gordon
authors.affiliation: SWOG Statistical Center, Seattle.
authors.forename: H M
authors.initials: HM
authors.lastname: Gundacker
authors.affiliation: SWOG Statistical Center, Seattle.
authors.forename: J
authors.initials: J
authors.lastname: Benedetti
authors.affiliation: Aptium Oncology, Inc., Los Angeles.
authors.forename: J S
authors.initials: JS
authors.lastname: Macdonald
authors.affiliation: University of Kansas Cancer Center, Westwood.
authors.forename: J C
authors.initials: JC
authors.lastname: Baranda
authors.affiliation: Pfizer, Inc., San Diego.
authors.forename: W J
authors.initials: WJ
authors.lastname: Levin
authors.affiliation: Department of Medicine, Knight Cancer Institute, Oregon Health and Science University, Portland.
authors.forename: C D
authors.initials: CD
authors.lastname: Blanke
authors.affiliation: Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles.
authors.forename: W
authors.initials: W
authors.lastname: Elatre
authors.affiliation: Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles.
authors.forename: P
authors.initials: P
authors.lastname: Weng
authors.affiliation: Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles.
authors.forename: J Y
authors.initials: JY
authors.lastname: Zhou
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lenz
authors.affiliation: Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles. Electronic address: press@usc.edu.
authors.forename: M F
authors.initials: MF
authors.lastname: Press
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D059186:Chemoradiotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005743:Gastrectomy; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: 5FU chemotherapy; FISH; HER2; gastric cancer; immunohistochemistry; radiation therapy