Abstract 2874: A prospective study of a repeat endoscopic biopsy to identify HER2-positive tumors following an initial HER2-negative endoscopic biopsy in unresectable or metastatic gastric cancer patients: GASTHER1 study
Authors: Park Sook Ryun , Park Young Soo , Ryoo Baek-Yeol , Woo Chang Gok , Jung Hwoon-Yong , Lee Jeong Hoon , Lee Gin Hyug , Ryu Min-Hee , Kang Yoon-Koo 
Published: May 2015

Abstract
Background: The intratumoral heterogeneity of HER2 expression in gastric cancer (GC) is a major challenge when identifying patients who will benefit from HER2-targeting therapy. The aim of this study is to evaluate the significance of re-evaluation of the HER2 status by repeat endoscopic biopsy in GC patients with an initial, HER2-negative endoscopic biopsy.
Methods: Patients with unresectable or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma and who will receive first-line chemotherapy, were eligible if the HER2 was negative on the initial endoscopic biopsy. HER2 positivity was defined as immunohistochemistry (IHC) 3+ or IHC 2+/fluorescence in situ hybridization (FISH) + using the GC scoring system. A repeat endoscopic biopsy was performed in ≥6 different primary tumor sites immediately after obtaining initial HER2-negative results.
Results: From May 2011 to April 2013, a total of 183 eligible patients were enrolled. Baseline characteristics at the time of the initial biopsy were as follows: tumor location, GEJ∼fundus/body/antrum/diffuse stomach=22(12.0%)/47(25.7%)/68(37.2%)/46(25.1%); Lauren classification, intestinal/diffuse/mixed=53(29.0%)/111(60.7%)/19(10.4%); and HER2 IHC score, 0/1/2=149(81.4%)/26(14.2%)/8(4.4%). The median number of biopsy pieces per patient was 5 (range, 1-15) and 10 (range, 1-15) on the initial and repeat biopsy, respectively (P&lt;0.0001). There was no difference in the median ratio of the number of cancer-containing pieces/total pieces; 0.86 (range, 0.13-1) vs. 0.89 (range, 0.10-1) (P=0.679). As the repeat biopsy identified 16 patients with HER2-positive tumor, the rate of rescued HER2 positivity was 8.7% (95% CI 4.6-12.8%). Rescued HER2 positivity was associated with tumor location (diffuse stomach vs. others=0% vs. 11.7%, P=0.013), Bormann type (IV vs. others=0% vs. 11.7%, P=0.013), and the HER2 IHC score on the initial biopsy (0 vs. 1 vs. 2 = 6.7% vs. 15.4% vs. 25.0%, P=0.028). In multivariate analysis, the HER2 IHC score (1/2 vs. 0, odds ratio=3.78; P=0.016) was an independent predictive factor for rescued HER2 positivity.
Conclusions: Repeat endoscopic biopsy is recommended in order to check the HER2 status again even if the initial endoscopic biopsy is HER2 negative in metastatic or unresectable GC.
Note: This abstract was not presented at the meeting.
Citation Format: Sook Ryun Park, Young Soo Park, Baek-Yeol Ryoo, Chang Gok Woo, Hwoon-Yong Jung, Jeong Hoon Lee, Gin Hyug Lee, Min-Hee Ryu, Yoon-Koo Kang. A prospective study of a repeat endoscopic biopsy to identify HER2-positive tumors following an initial HER2-negative endoscopic biopsy in unresectable or metastatic gastric cancer patients: GASTHER1 study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2874. doi:10.1158/1538-7445.AM2014-2874