title: Poor efficacy response to trastuzumab therapy in advanced gastric cancer with homogeneous HER2 positive and non-intestinal type.
abstract: BACKGROUND
  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).
  
  
  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 trastuzumabx which is homogeneous HER2 positive and non-intestinal type.
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Dongxian
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jieakesu
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yingyong
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000074322:Antineoplastic Agents, Immunological; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
keywords: HER2; efficacy; gastric cancer; heterogeneity; trastuzumab