The expand indication of HER2 targeted therapies by monitoring of circulating tumor cells.

482 Background: Despite success in the HER2 targeted therapies for metastatic gastric cancer patients, the conventional assessment of HER2 status in tumor tissue specimens is still under debate. Methods: On-chip sorting system was used for the isolation of circulating tumor cells (CTCs). The fluorescence signal intensity > 50 is set to be a threshold value for distinguishing between positive and negative HER2 on CTCs. Epithelial mesenchymal transition (EMT) was assessed by the vimentin and cytokeratin. DNA was extracted from CTCs and applied to the cancer gene panel. Results: In 27 patients with metastatic gastric cancer, 13 patients showed HER2 positive in tumor tissues (Group A) who were treated with cytotoxic agents and HER2-targeted therapy while 14 patients exhibited negative and treated with cytotoxic agents. In these 14 patients, 8 patients showed HER2 positive (Group B) and 6 patients displayed HER2 negative (Group C) on CTCs. HER2 expression on CTCs was associated with EMT (p<0.001). Increased expression of EMT was seen in Group A and B, indicating they are likely to have metastasis. Group B exhibited worse PFS than others (13.8 M in A, 7.0 M in B and not reached in C, p=0.012). In addition, genomic analysis identified cancer gene mutations, some of which were involved in mechanisms underlying EMT and were shared between Group A and B. Considering HER2 expression on CTCs in Group B, an additional HER2-targeted therapy may be beneficial. Conclusions: Our study suggests that monitoring of circulating tumor cells leads to the expand indication of the HER2 targeted therapies in patients with metastatic gastric cancer.