Aspirin to inhibit the formation and EMT of circulating tumor cells in patients with metastatic colorectal cancer but not breast cancer.

Abstract

e23024 Background: High circulating tumor cells (CTCS) have been acknowledged as a poor indication in malignant disease. Besides, platelets are found play crucial role in tumor cells’ epithelial – mesenchymal transition and metastasis, so here we test if disruption of platelet function with aspirin, could decrease the number and inhibit the EMT of CTCs in metastatic colorectal (MCC) or breast cancer (MBC). Methods: Patients with MCC or MBC who were not receiving cytotoxic chemotherapy currently (except for capecitabine maintenance), while endocrine therapy, bisphosphonate or molecular targeted therapy were accepted. Base line of Platelet aggregation rate (PAR), CTCs’ number and molecular phenotype were recorded. Patients whose CTCs ≥ 5 cells/7.5ml peripheral blood were included and receive aspirin 100mg/day for the following 8 weeks. Then the phlebotomy was performed at 4, 8 weeks thereafter to obtain specimen and assess PAR, CTCs’ number and phenotype. The phenotypes of CTCs were classified into epithelial (E+), mesenchymal(M+) and middle type(express both E+ and M+ markers) with fluorescence in situ hybridization assay. Results: Forty patients (19 MBC and 21 MCC patients ) were enrolled. Base line CTC numbers were 8.7± 3.4 in MBC patients, the ratio of E+ and M+ type were 48.2 ± 22.4% and 25.1 ± 14.9% respectively; the base line CTC numbers were 10.7 ± 4.8 in MCC patients, and the ratio of E+ and M+ type were 45.3 ± 27.3% and 22.0 ± 18.5% respectively. Despite adequate platelets inhibition in both groups, CTC numbers were similar in MBC patients in the following 8 weeks ( p= 0.0532 ), while the fraction of E+ or M+ CTCs were also unchanged (E+ CTCs p= 0.305; M+ CTCs p= 0.09); however, both CTC numbers and fraction of M+CTCs were markedly decreased in MCC patients (total numbers: p< 0.01; E+ CTCs p= 0.031; M+ CTCs p= 0.013) . Conclusions: Aspirin could decreased the number of CTCs and block EMT transition in MCC patients, and our results provide potential explanation of how aspirin impede the metastasis of colorectal cancer. But this effect could not be observed in MBC patients. Future studies evaluating the underlying mechanism of this differences remain of interest, and they may be informed by our results. Clinical trial information: NCT02602938.