Poor efficacy response to trastuzumab therapy in advanced gastric cancer with homogeneous HER2 positive and non-intestinal type

// Chen Xu 1, 2, * , Yalan Liu 1, 2, * , Dongxian Jiang 1, 2 , Qian Li 3 , Xiaowen Ge 1, 2 , Ying Zhang 1, 2 , Jie Huang 1, 2 , Jieakesu Su 1, 2 , Yuan Ji 1, 2 , Jun Hou 1, 2 , Shaohua Lu 1, 2 , Yingyong Hou 1, 2 , Tianshu Liu 3 1 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China 2 Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China 3 Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China * These authors contributed equally to this work Correspondence to: Yingyong Hou, email: houyingyong@aliyun.com Tianshu Liu, email: liu.tianshu@zs-hospital.sh.cn Keywords: gastric cancer, HER2, heterogeneity, trastuzumab, efficacy Received: December 16, 2016      Accepted: March 16, 2017      Published: March 25, 2017 ABSTRACT Introduction: Factors affecting trastuzumab efficacy in advanced gastric cancer (GC) are largely unknown. Heterogeneity is a notable feature of HER2 in GC. Whether the heterogeneity influences trastuzumab efficacy is still unknown. Results: The HER2 homogeneous group and HER2 heterogeneous group showed no statistical difference in RR (46.4% vs 55.0%, P = 0.558), PFS (5.80 vs 6.30 months, P = 0.804) and OS (16.00 vs 16.00 months, P = 0.787). The Lauren intestinal group and Lauren non-intestinal group demonstrated no discrepancy in PFS (6.00 vs 6.00 months, P = 0.912) and OS (16.50 vs 14.00 months, P = 0.227). However, by combining HER2 heterogeneity and Lauren classification, PFS and OS of HER2 homogeneous /Lauren non-intestinal subgroup was the shortest among the 4 subgroups ( P = 0.012 and P = 0.037), which was much shorter than the other patients (PFS:3.00 vs 6.30 months, P = 0.003; OS: 4.50 vs 16.50 months, P = 0.004). Univariate and multivariate analysis showed that HER2 heterogeneity combined with Lauren classification was an independent prognostic factor in both PFS ( P = 0.031 and P = 0.002) and OS ( P = 0.039 and P = 0.013). Materials and Methods: 48 patients with HER2 positive advanced GCs accepting trastuzumab treatment were retrospectively analyzed. Based on HER2 heterogeneity, the patients were divided into a HER2 homogeneous group and a HER2 heterogeneous group. Response rate (RR), progression free survival (PFS), and overall survival (OS) were compared. Main clinicopathological factors including Lauren classification were subjected to subgroup analysis. Conclusions: HER2 heterogeneity alone may not correlate with trastuzumab efficacy in HER2 positive advanced GCs. HER2 heterogeneity combined with Lauren classification may help to identify a subgroup with poor response to trastuzumab which is homogeneous HER2 positive and non-intestinal type.