Abstract

BackgroundEribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker.MethodsTILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively.ResultsOf the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063).ConclusionThe results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.

Highlights

  • Eribulin mesylate stops cell division by inhibiting microtubule extension [1,2,3], and has a mechanism of action that differs from other antimitotic drugs such as taxane and vinca alkaloids [2, 4, 5]

  • We thought that eribulin, which has an epithelial-mesenchymal transition (EMT)-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with Tumor-infiltrating lymphocytes (TILs) as a marker

  • In an analysis of outcomes, triple-negative breast cancer (TNBC) patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank)

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Summary

Introduction

Eribulin mesylate (eribulin) stops cell division by inhibiting microtubule extension [1,2,3], and has a mechanism of action that differs from other antimitotic drugs such as taxane and vinca alkaloids [2, 4, 5]. In a phase III trial of eribulin (EMBRACE, Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice versus E7389), a significant prolongation of overall survival was observed in patients with locally advanced or metastatic breast cancer (MBC) after eribulin treatment even without an improvement in disease free survival [6]. This effect was partially explained by a decrease in the occurrence of new metastatic lesions with eribulin therapy, an effect that has not been demonstrated with other drugs. Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC) It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker

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