Chemotherapy administration to breast cancer patients affects extracellular vesicles thrombogenicity and function

Breast cancer (BC) is the most prevalent type of malignancy in women. Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles. STUDY AIMS To elucidate the effects of chemotherapy administration on BC patients' EVs characteristics and their effects on endothelial cells (EC) functions. METHODS EVs were isolated from the blood samples of 54 BC patients treated by chemotherapy (25 neo-adjuvant, 29 adjuvant) and from 20 healthy women (control group). Blood samples were taken before chemotherapy and on the day of last chemotherapy administration. In some patients, samples were also evaluated 24 hours after chemotherapy treatment. EVs were characterized by cell origin, thrombogenicity and cytokine content. EVs effects on coagulation, migration, apoptosis and proliferation of endothelial cells were assessed as well. RESULTS Patient characteristics of the two subgroups were similar except for tumor size. Change in EV expression of BC markers, MUC1 and EpCAM, were found in patient subgroups. EC-EVs were significantly higher in both patient subgroups compared to healthy controls. Higher EVs pro-coagulant activity was found at the end of chemotherapy and a significant increase in the ratio between tissue factor (TF) and TF pathway inhibitor was documented after the first 24hours of exposure to doxorubicin treatment. Furthermore, EVs of neo-adjuvant patients obtained before chemotherapy contained more pro-angiogenic proteins, reduced endothelial cells apoptosis and increased their migration compared to EVs obtained at the same timing from adjuvant patients. CONCLUSIONS EVs may serve as a biomarker for chemotherapy-related thrombogenicity and may indicate vascular damage even before chemotherapy.