title: HER2 Status in Gastric and Gastroesophageal Junction Cancer: Results of the Large, Multinational HER-EAGLE Study.
abstract: Human epidermal growth factor receptor 2 (HER2) dysregulation is associated with tumorigenesis in gastric/gastroesophageal junction cancer; however, the number of patients with HER2-positive disease is unclear, possibly due to differing scoring criteria/assays. Data are also lacking for early disease. We aimed to assess the HER2-positivity rate using approved testing criteria in a large, real-life multinational population. HER2-positivity was defined as an immunohistochemistry staining score of 3+, or immunohistochemistry 2+ and HER2 amplification detected by in situ hybridization. A total of 4949 patients were enrolled and results showed that 14.2% of 4920 samples with immunohistochemistry results were HER2-positive. HER2-positivity was significantly higher in males (16.1% vs. 9.6% in females), in gastroesophageal versus stomach tumors (22.1% vs. 12.9%), in biopsy versus surgical samples (18.3% vs. 13.0%), in intestinal tumor subtypes versus diffuse (21.5% vs. 4.8%) and mixed types (21.5% vs. 8.5%) (P<0.001), in mixed versus diffuse types (8.5% vs. 4.8%), and in "other" versus diffuse types (11.7% vs. 4.8%; P=0.002). There were no significant differences between stages. Patients in the youngest age percentile had significantly lower HER2-positivity rates than patients in the remaining percentiles (9.2% vs. 15.9%, 15.7%, and 15.1%; P<0.001). HER2-positivity was highest in France (20.2%) and lowest in Hong Kong (10.4%). In conclusion, HER-EAGLE, the first study of its kind to be conducted in a large, multinational population of almost 5000 patients, gives valuable insights into the real-world HER2-positivity rate in a gastric/gastroesophageal junction cancer patient population not selected for disease stage or histology.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Woo-Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Anatomical Pathology, Hospital Universitario Virgen del Rocio, Seville, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Gomez-Izquierdo
authors.affiliation: Anatomical Pathology Service, Hospital Universitari Arnau de Vilanova de Lleida and IRBLleida, Lleida, Spain.
authors.forename: Felip
authors.initials: F
authors.lastname: Vilardell
authors.affiliation: Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Kent-Man
authors.initials: KM
authors.lastname: Chu
authors.affiliation: Pathology Department, Hôpital Saint-Luc du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Soucy
authors.affiliation: Instituto de Ensino e Pesquisa São Lucas and Clinical Research Unit, Barretos Cancer Hospital, São Paulo, Brazil.
authors.forename: Lucas V
authors.initials: LV
authors.lastname: Dos Santos
authors.affiliation: Department of Pathology, Centre Hospitalier Universitaire de Nice, Hôpital Pasteur, Nice, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Monges
authors.affiliation: Department of Pathology, European Institute of Oncology, University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.affiliation: Department of Pathology, Hospital Garcia de Orta, Almada, Portugal.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Brito
authors.affiliation: GMA Biometrics, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Stuart
authors.initials: S
authors.lastname: Osborne
authors.affiliation: Oncology Biomarker Development, Genentech, Basel, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Noé
authors.affiliation: Department of Pathology, Cancer Center of Fudan University and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
mesh_terms: D000367:Age Factors; D000368:Aged; D001208:Asia / Q000453:epidemiology; D001938:Brazil / Q000453:epidemiology; D002170:Canada / Q000453:epidemiology; D055088:Early Detection of Cancer; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000378:metabolism*; D004943:Esophagogastric Junction / Q000473:pathology*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000378:metabolism*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human