title: HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer.
abstract: BACKGROUND
  In the Trastuzumab for GAstric cancer (ToGA) study, trastuzumab plus chemotherapy improved median overall survival by 2.7 months in patients with human epidermal growth factor receptor 2 (HER2)-positive [immunohistochemistry (IHC) 3+/fluorescence in situ hybridization-positive] gastric/gastroesophageal junction cancer compared with chemotherapy alone (hazard ratio 0.74). Post hoc exploratory analyses in patients expressing higher HER2 levels (IHC 2+/fluorescence in situ hybridization-positive or IHC 3+) demonstrated a 4.2-month improvement in median overall survival with trastuzumab (hazard ratio 0.65). The ToGA study provides the largest screening dataset available on HER2 overexpression/amplification in this indication. We further analyzed correlation(s) of HER2 overexpression/amplification with clinical and epidemiological factors.
  
  
  METHODS
  HER2-positivity was analyzed by histological subtype, tumor location, geographic region, and specimen type. Exploratory efficacy analyses were performed.
  
  
  RESULTS
  The HER2-positivity rate was 22.1 % across analyzed tumor samples. Rates were similar between European and Asian patients (23.6 % vs. 23.9 %), but higher in intestinal- vs. diffuse-type (31.8 % vs. 6.1 %), and gastroesophageal junction cancer versus gastric tumors (32.2 % vs. 21.4 %). Across all IHC scores, variability in HER2 staining (≤30 % stained cells) was observed in almost 50 % of cases, with increasing rates in lower IHC categories, and did not affect treatment outcome. The polysomy rate was 4 %.
  
  
  CONCLUSIONS
  HER2 expression varies by tumor location and type. All patients with advanced gastric or gastroesophageal junction cancer should be tested for HER2 status, preferably using IHC initially. Due to the unique characteristics of gastric cancer, specific testing/scoring guidelines should be adhered to.
authors.affiliation: University Hospitals Leuven and KU Leuven, Leuven, Belgium, eric.vancutsem@uzleuven.be.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.forename: Feng
authors.initials: F
authors.lastname: Feng-Yi
authors.forename: Jian M
authors.initials: JM
authors.lastname: Xu
authors.forename: Keun-Wook
authors.initials: KW
authors.lastname: Lee
authors.forename: Shun-Chang
authors.initials: SC
authors.lastname: Jiao
authors.forename: Jorge León
authors.initials: JL
authors.lastname: Chong
authors.forename: Roberto I
authors.initials: RI
authors.lastname: López-Sanchez
authors.forename: Timothy
authors.initials: T
authors.lastname: Price
authors.forename: Oleg
authors.initials: O
authors.lastname: Gladkov
authors.forename: Oliver
authors.initials: O
authors.lastname: Stoss
authors.forename: Julie
authors.initials: J
authors.lastname: Hill
authors.forename: Vivian
authors.initials: V
authors.lastname: Ng
authors.forename: Michaela
authors.initials: M
authors.lastname: Lehle
authors.forename: Marlene
authors.initials: M
authors.lastname: Thomas
authors.forename: Astrid
authors.initials: A
authors.lastname: Kiermaier
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D058990:Molecular Targeted Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000068878:Trastuzumab / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human