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Poster display session

1791 - Change in the molecular profile of tumor tissues during treatment with trastuzumab, as analyzed by next-generation sequencing and immunohistochemistry—A multicenter prospective biomarker study on HER2-positive gastric cancer


09 Sep 2017


Poster display session


Cytotoxic Therapy;  Targeted Therapy;  Translational Research;  Gastric Cancer


Naoki Takahashi


Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369


N. Takahashi1, S. Iwasa2, T. Sawada3, Y. Sasaki4, H. Taniguchi5, I. Oda6, T. Honda7, Y. Kojima8, H. Hara9, Y. Honma2, A. Takashima2, K. Kato10, T. Hamaguchi11, Y. Yamada12

Author affiliations

  • 1 Department Of Gastroenterology, Saitama Cancer Center, 362-0806 - Ina-machi, Kita-Adachi-gun/JP
  • 2 Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo/JP
  • 3 Department Of Advanced Research In Community Medicine, Kanazawa University, 920-8641 - Kanazawa/JP
  • 4 Department Of Medical Genome Sciences, Research Institute For Frontier Medicine, Sapporo Medical University, Hokkaido/JP
  • 5 Pathology And Clinical Laboratory Division, National Cancer Center Hospital, Tokyo/JP
  • 6 Endoscopy Division, National Cancer Center Hospital, Tokyo/JP
  • 7 Gastroenterology And Hepatology, Nagaski University Hospital, 852-8501 - Nagasaki/JP
  • 8 Department Of Gastroenterology, National Center for Global Health and Medicine, Tokyo/JP
  • 9 Department Of Gastroenterology, Saitama Cancer Center Hospital, Saitama/JP
  • 10 Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 11 Gastrointestinal Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 12 Department Of Clinical Oncology, Hamamatsu University, Shizuoka/JP


Abstract 1791


Trastuzumab (Tmab) is an active molecular-targeted drug for HER2-positive gastric cancer (GC) patients. However, continued use of Tmab beyond progression is not established in HER2-positive GC, unlike that of breast cancer. Therefore, we conducted this study to evaluate the resistance mechanism of anti-HER2 drugs in metastatic GC patients.


Metastatic HER2-positive GC patients treated with Tmab were registered prospectively, and tumor tissues were obtained by biopsy from primary lesions at the following points: (1) pre-treatment, (2) post-treatment, and (3) disease progression during chemotherapy with Tmab. Formalin-fixed paraffin-embedded tissue slides were prepared, and the expression of receptor tyrosine kinases (RTKs) such as EGFR, HER2, HER3, c-MET, FGFR2 and IGF-1R was evaluated by immunohistochemistry (IHC). Hot spot mutations and copy number variations (CNVs) were analyzed by next-generation sequencing (NGS) using Ion AmpliSeq Cancer Hotspot Panel v2.


Twenty patients were enrolled and evaluated by IHC, and 15 of 20 patients were evaluated by NGS. One patient was excluded because HER2 status was revealed as negative after registration. HER2 expression (≥2+) by IHC have disappeared after treatment in 8 patients (42%). FGFR2 expression (≥2+) by IHC was most frequently observed after treatment. Cases with IGF-1R expression (≥2+) were significantly increased after treatment (p 


Our study indicated that molecular changes in RTK expression and genomic alternation frequently occur during treatment with Tmab. These findings will contribute to the development of individualized treatment for HER2-positive GC patients.

Clinical trial identification

UMIN000006454 (Japan). Release date is 03/October/2011.

Legal entity responsible for the study

National Cancer Center, Tokyo


Grants‐in‐aid for Scientific Research


All authors have declared no conflicts of interest.

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