Abstract 4100: Epithelial-mesenchymal transition and tumor vascular remodeling in eribulin chemotherapy for breast cancer

Abstract

Abstract Purpose: Eribulin mesylate (eribulin) is a promising chemotherapeutic agent to treat locally advanced or metastatic breast cancer (MBC). Not only its cytotoxic efficacy, but its unique mechanisms to suppress epithelial-mesenchymal transition (EMT) of the cancer cells, or to promote tumor vascular remodeling attracted attention in basic models. In this study, we investigated markers of EMT and hypoxia in sets of clinical specimens before and after treatment of eribulin in an aim to verify its profound mechanisms. Experimental Design: A series of 20 sets of the tissue specimens of MBC obtained before and after chemotherapy from patients treated either with eribulin (n = 10), or with paclitaxel (n = 10) were immunohistochemically investigated with the expression of E-cadherin, N-cadherin, Vimentin, and CA9. The cut-off for E-cadherin positivity was >30% positive tumor cells with membrane staining. The cut-off for N-cadherin and Vimentin positivity were >10% positive tumor cells with cytoplasm staining. And, the cut-off for CA9 positivity was >10% positive tumor cells with membrane staining. Results: Looking at the relation between the transition in this protein expression and therapeutic effect, cases observed with positive conversion in E-cadherin expression and cases observed with negative conversion in CA9 expression had significantly high response rate (RR) (p = 0.004, p = 0.024). Among high RR cases, E-cadherin expression was remarkably increased, the N-cadherin, Vimentin and CA9 expression were reduced. A significant prolongation of progression-free survival (PFS) was observed in patients with tumor showed E-cadherin positive-conversion (p = 0.041, log-rank). Significantly longer periods of time to treatment-failure (TTF) were achieved in patients with tumors showed E-cadherin positive-conversion (p = 0.018, log-rank) or showed CA9 negative-conversion (p = 0.038, log-rank). There was no difference in over-all survival (OS) of the patients when stratified with the expression of and change in EMT markers. No difference was observed either in PFS, TTF, or OS of the patients according to the expressions of and change in N-cadherin and Vimentin.Conclusions: Increased expression of E-cadherin was observed along with reduced expression of N-cadherin, Vimentin, and CA9, EMT suppression was caused by eribulin chemotherapy, and further, it was suggested that vascular remodeling may have been induced. Citation Format: Kashiwagi Shinichiro, Yuka Asano, Yukie Tauchi, Tokumoto Mao, Tamami Morisaki, Satoru Noda, Hidemi Kawajiri, Tsutomu Takashima, Naoyoshi Onoda, Kosei Hirakawa. Epithelial-mesenchymal transition and tumor vascular remodeling in eribulin chemotherapy for breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4100. doi:10.1158/1538-7445.AM2015-4100