HER2 Status in Gastric and Gastroesophageal Junction Cancer: Results of the Large, Multinational HER-EAGLE Study.

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.