Clinical significance of circulating tumor cells in the response to trastuzumab for HER2-negative metastatic gastric cancer

Purpose The prognosis of metastatic gastric cancer has improved due to trastuzumab in patients with HER2 positive. Circulating tumor cells (CTCs) have been examined as a prognostic predictor in gastric cancer. The clinical advantage of trastuzumab was examined in gastric cancer patients with HER2-negative tumor tissues and HER2-positive CTCs. Methods A total of 105 patients with metastatic or recurrence gastric cancer were enrolled. All patients were examined HER2 expression in CTC using the CellSearch system in blood specimens. Results CTCs were detected in 65 of 105 patients (61.9%) and 61 patients were divided into three groups: Group A ( n = 27), histological HER2-positive; Group B ( n = 17), histological HER2-negative and HER2-positive CTCs; and Group C ( n = 17), HER2-negative on histology and CTCs. Patients received capecitabine plus cisplatin. Groups A and B were additionally treated by trastuzumab. There was no relationship between tumor tissues and CTCs in HER2 expression. Even if group B had no histological HER2 expression, group B showed a good prognosis as same as group A, and group C had a significantly worse overall survival than groups A and B. The multivariate analysis demonstrated that HER2-expression on CTCs was an independent prognostic factor for both overall and progression-free survival. Conclusion The present results indicate the potential clinical utility of trastuzumab combined chemotherapy in patients with HER2-positive CTCs even if they are histologically HER2-negative.