Research Papers:

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

Chen Xu, Yalan Liu, Dongxian Jiang, Qian Li, Xiaowen Ge, Ying Zhang, Jie Huang, Jieakesu Su, Yuan Ji, Jun Hou, Shaohua Lu, Yingyong Hou and Tianshu Liu _

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Oncotarget. 2017; 8:33185-33196. https://doi.org/10.18632/oncotarget.16567

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Chen Xu1,2,*, Yalan Liu1,2,*, Dongxian Jiang1,2, Qian Li3, Xiaowen Ge1,2, Ying Zhang1,2, Jie Huang1,2, Jieakesu Su1,2, Yuan Ji1,2, Jun Hou1,2, Shaohua Lu1,2, Yingyong Hou1,2, Tianshu Liu3

1Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China

2Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China

3Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China

*These authors contributed equally to this work

Correspondence to:

Yingyong Hou, email: [email protected]

Tianshu Liu, email: [email protected]

Keywords: gastric cancer, HER2, heterogeneity, trastuzumab, efficacy

Received: December 16, 2016     Accepted: March 16, 2017     Published: March 25, 2017


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 HER2homogeneous group and HER2heterogeneous 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 Laurenintestinal group and Laurennon-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 HER2homogeneous/Laurennon-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 HER2homogeneous group and a HER2heterogeneous 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.

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