Assessment of HER2 status from an epidemiology study in tumor tissue samples of gastric and gastro-esophageal junction cancer: Results from the french cohort of the HER-EAGLE study.

Abstract

26 Background: HER2 is an important prognostic and also a predictive biomarker for trastuzumab response in gastric cancer. Therefore, HER2 status should be tested in all gastro-esophageal junction (GEJ) and gastric cancer (GC) patients. ToGA phase III study showed a benefit in overall survival of trastuzumab added to standard chemotherapy in patients with HER2-positive advanced GEJ/GC. The objective of the HER-EAGLE study was to assess the incidence of HER2 positivity in GEJ/GC cancer. Methods: HER-EAGLE was an international epidemiological, non-interventional study assessing HER2 status by IHC/ISH in tumor samples from any stage in patients with GEJ/GC. Samples were obtained by excision or core biopsy and routinely analyzed via validated Ventana or Dako methods and scoring criteria used in ToGA: HER2-positive if IHC 3+ or IHC 2+ (FISH/SISH confirmed; HER2/CEP17 ratio ≥ 2.0); HER2-negative if IHC 0 or IHC 1+ or IHC 2+ if FISH/SISH negative ratio < 2.0. Overall and subgroup estimates calculated with 95% CI. Data from the French cohort are presented. Results: The HER-EAGLE French cohort included 267 patients (68.6% males) from 7 centers (May 2007 to March 2012), with 150 biopsies (56.2%) and 117 excisions (43.8%). Tumor locations were 65.9% stomach and 34.1% GEJ, and adenocarcinoma types were according to Lauren classification: 170 intestinal (63.7%), 72 diffused (27%), 22 mixed (8.2%) and 3 not available (1.1%). HER2 status was: 36 cases IHC 3+ (13.5%), 51 IHC 2+ (19.1%) whereof 18 ISH positive (35.3%), 35 IHC 1+ (13.1%) and 145 IHC 0 (54.3%). Overall HER2 positivity (IHC 3+ or IHC 2+/ISH+) was 20.2%. Heterogeneity for HER2 staining was observed in 81 samples (30.3%). No statistical difference was found according to cancer stage. HER2 positivity was higher in GEJ (31.9%) than in GC (14.2%), p<0,001, and higher in intestinal (28.2%) compared to diffused adenocarcinomas (5.6%), p<0,001. Conclusions: HER-EAGLE French cohort results confirmed the feasibility of HER2 testing in GEJ/GC in routine practice. The incidence of HER2 overexpression was similar to the literature review, and it was higher in GEJ and intestinal adenocarcinomas type.