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

Abstract

BackgroundAnticancer 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.MethodsTGF-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 (T0), after four cycles of eribulin (T1) and at disease progression (TPD). Baseline values and longitudinal changes in cytokine levels were then related to clinical outcome.ResultsIn the 41 patients, high IL-6 and IL-8 (above the median) at T0 significantly correlated with worse survival. At T1, IL-21 significantly decreased in patients with TPD 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 T1 significantly correlates with worse progression free survival (PFS). Patients exhibiting an increase of TGF-β or a decline of IL-21 between T0 and T1 showed a significantly worse PFS. Multivariate Cox regression analysis showed that only plasma TGF-β changes at T1 correlated with survival. At TPD, TGF-β significantly increased in all patients.ConclusionsWe 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.

Cytokine Profiling of End Stage Cancer Patients Treated with Immunotherapy

“…Similarly, IL-8 high plasma levels were widely associated with poor OS [ 17 , 18 ]. Looking at the longitudinal analysis, only the progressive increase of IL-10 at each time point correlated with a significant reduction of survival, reinforcing the negative role of this IL [ 19 ].…”

Circulating Cytokines in Metastatic Breast Cancer Patients Select Different Prognostic Groups and Patients Who Might Benefit from Treatment beyond Progression

“…Finally, in mBC patients treated with eribulin, a significant decrease of TGF-β leads to a better outcome [13].…”

Eribulin and Paclitaxel Differentially Alter Extracellular Vesicles and Their Cargo from Triple-Negative Breast Cancer Cells

“…These effects were not observed with the microtubule stabilizer paclitaxel, demonstrating that MTAs can have distinct microtubule-dependent consequences on oncogenic pathways that could be associated with their clinical efficacies. There is also evidence that effects on the tumor microenvironment are important predictors of response to MTAs, for example, in metastatic breast cancer patients treated with eribulin, those who had a decrease in circulating TGF-β post treatment had significantly improved progression-free survival [ 37 ]. Additionally, eribulin has been shown to remodel abnormal tumor vasculature in patients [ 38 ] and in preclinical models, where this effect correlated strongly with tumor regression [ 39 ].…”