Abstract 4137: Circulating TGFâ and TNFá in metastatic breast cancer patients treated with eribulin. The TRANSERI project

Abstract

Abstract Background: Eribulin (E) is approved for the treatment of metastatic breast cancer (mBC) patients (pts) after failure of antracyclines and taxanes. E interferes with microtubule leading to apoptosis and G2/M cell cycle arrest. In human cancer cell lines and in mice, it reverses epithelial mesenchimal transition (EMT) and reduces metastases in mice. TGFβ, an immunosuppressive cytokine, acts as growth factor for cancer-associated fibroblasts (CAFs) and promotes EMT. TNFα synergizes with TGFβ to promote EMT. The TRANSERI study investigates the modifications of TGFβ and TNFα levels in 40 mBC pts treated with E. Methods: Plasma levels of TGFβ and TNFα were determined by ELISA assay at baseline, before cycle (C) 3, 5 and at disease progression in mBC pts treated with E at 1.23 mg/m2, d 1-8 every 21 d. Statistical analysis of the changes in the longitudinal samples was performed by GraphPad 5. Clinical outcome was monitored according to standard internal follow up procedure. Results: We report analyses in pts who completed 5 C or progressed before C 5. So far, we have evaluated TGFβ level in 34 pts and TNFα in 26 pts. The median (M) basal TGFβ value was higher in pts than in 9 healthy volunteers (201.9 pg/ml vs 115.1 respectively). At C 5, 14 pts had a decrease in TGFβ with a M value approaching the one of healthy controls (161.9 pg/ml vs 115.1 pg/ml respectively). 19 pts progressed before C 5. Overall 26/33 pts experienced progression. The M value of TGFβ in pts at progression was 293.4 pg/ml. A significant difference of TGFβ was observed between non progressed vs progressed pts (p=0.021). The M TNFα value at baseline was higher in pts than in healthy volunteers, even if in both groups it was close to the lower sensitivity cut-off of the assay. Altogether 20/26 pts experienced progression, that occurred before C 5 in 14 out of them.Intriguingly, at C 5, the TNFα / TGFβ ratio was significantly lower in pts who did not progressed compared to the value at progression (p=0.048). Conclusions: TGFβ levels changed during treatment with E and correlate with outcome. We are evaluating the role of tumor burden in modulating the TNFα / TGFβ ratio. Definitive data will be presented. Citation Format: Ornella Garrone, Cristiana Lo Nigro, Andrea Michelotti, Fillippo Montemurro, Anna Maria Vandone, Andrea Abbona, Matteo Paccagnella, Antonella Falletta, Elena Genua, Claudia De Angelis, Federica Tonissi, Paola Vanella. Circulating TGFâ and TNFá in metastatic breast cancer patients treated with eribulin. The TRANSERI project [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4137.