Circulating endothelial microparticles (EMP) modifications as predictive biomarkers of resistance to chemotherapy for breast cancer (BC).

Abstract

3042 Background: Growing evidence indicates that EMP may both modulate angiogenesis and endothelial injury in cancer and cardiovascular disease. However, it has not been shown whether in vivo release of EMP might reflect the tumor response or the antiangiogenic effects of chemotherapy (CT). The aim of this work was to evaluate the relationship between the levels of small-size EMP (sEMP) and resistance to CT in locally advanced and metastatic BC. Methods: Citrated platelet-free plasma was obtained from BC patients before and after 3-4 cycles of chemotherapy. Small-size CD144+ sEMP (0.1-0.5 μm diameter) were prospectively quantified using a high resolution Apogee A50 flow cytometer. Association of EMP with clinical variables, response to CT and survival was analyzed. Response (partial or complete) was defined by RECIST criteria. Results: 45 BC patients were included (20, metastatic; 25, locally advanced). Treatment included anthracyclines in 66.7% of patients and taxanes in 15.5%. Small-size EMP baseline counts were higher in premenopausal women (p=0.008), but no association with other clinical or pathological characteristic was found. A significant decrease of circulating sEMP was observed after treatment with CT in the whole group of patients with paired samples available (n=33): pre-CT: 416.2 ± 365 vs. post-CT: 340.7 ± 458 (p=0.005). Lower chemotherapy-induced sEMP decrease was associated to treatment resistance: ROC analysis demonstrated a 66.7% sensitivity and 72.2% specificity of lower sEMP decrease for lack of response to CT using a decline cut-point of -40 sEMP (close to median decrease: -47). With the same cut-point of low sEMP decrease, odds ratio for treatment resistance was 5.2 (95% confidence interval, 1.17-23.04; p=0.03). No clear association of the degree of sEMP decrease was found for disease or progression free survival in the neoadjuvant or in the metastatic setting. Conclusions: This study suggests that circulating sEMP decrease after CT and are tightly associated with treatment resistance in BC patients. These findings indicate pathophysiological roles for sEMP in BC and support their potential role as treatment resistance biomarkers.