Exploratory analysis of circulating cytokines in patients with metastatic breast cancer treated with eribulin: the TRANSERI-GONO (Gruppo Oncologico del Nord Ovest) study

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 beta (TGF-beta) 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-beta, tumour necrosis factor alpha, 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-beta 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-beta 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-beta changes at T(1)correlated with survival. At T(PD,)TGF-beta significantly increased in all patients. Conclusions We observed a significant correlation between TGF-beta 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.