Abstract
BACKGROUND: Anticancer drugs can interact with the tumour microenvironment and their effects could be exploited to favour anticancer immune response. Eribulin contributes to tumour vasculature remodelling and transforming growth factor β (TGF-β) modulation in experimental models and in humans. We performed a prospective, translational, exploratory analysis of the levels of circulating cytokines at different time points in patients with metastatic breast cancer treated with eribulin. METHODS: TGF-β, tumour necrosis factor α, vascular endothelial growth factor, IL-6, IL-8, IL-10, IL-21 and C-C motif chemokine ligand-2 levels were assessed in peripheral blood samples obtained from seven healthy volunteers and 41 patients at baseline (T(0)), after four cycles of eribulin (T(1)) and at disease progression (T(PD)). Baseline values and longitudinal changes in cytokine levels were then related to clinical outcome. RESULTS: In the 41 patients, high IL-6 and IL-8 (above the median) at T(0) significantly correlated with worse survival. At T(1), IL-21 significantly decreased in patients with T(PD) within the fourth course of treatment, compared with patients without progression. TGF-β and IL-8 above the median and IL-21 below the median at T(1) significantly correlates with worse progression free survival (PFS). Patients exhibiting an increase of TGF-β or a decline of IL-21 between T(0) and T(1) showed a significantly worse PFS. Multivariate Cox regression analysis showed that only plasma TGF-β changes at T(1) correlated with survival. At T(PD,) TGF-β significantly increased in all patients. CONCLUSIONS: We observed a significant correlation between TGF-β decline during eribulin treatment and outcome in patients with metastatic breast cancer. Altogether, our data suggest that eribulin treatment might interfere with the tumour microenvironment.