Abstract
ABSTRACT Aim: The recently developed reagent, eribulin mesylate (eribulin), is a microtubule dynamics inhibitor with a mechanism of action that differs from that of taxanes and vinca alkaloids. This drug is considered to be a promising chemotherapeutic agent for the treatment of locally advanced or metastatic breast cancer (MBC). In this study, we investigated predictive factors with respect to the therapeutic effect of eribulin chemotherapy among variables such as b-tubulin class III, GSTP1 and TLE3, which have previously been reported to be predictive factors of the therapeutic effect of taxanes, in an aim to identify possible biomarkers for predicting the efficacy of eribulin. Methods: The subjects included 52 patients with MBC who underwent chemotherapy using eribulin. The median follow-up time was 431 days (range, 50-650 days). The overall response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), overall survival (OS), time to treatment failure (TTF) and progression-free survival (PFS) were calculated regarding the efficacy of this regimen. Moreover, breast cancer was classified into intrinsic subtypes according to the status of the ER, PR, HER2 and Ki67 expression. Results: The clinical effects were as follows: overall ORR= 34.6%, CBR = 44.2%, DCR= 51.9%; median OS = 334 days; median TTF = 81 days; and median PFS = 275 days. TLE3, b-tubulin class III and GSTP1 were expressed in 24 cases, 21 cases and 24 cases, respectively, among the 52 patients investigated. The expression of TLE3 was found significantly more frequently in the TNBC lesions than in the non-TNBC lesions (p = 0.030). The patients with TLE3-negative tumors experienced significantly poorer outcomes in terms of progression-free survival when comparing the prognosis within the group of patients with triple-negative breast cancer (TNBC) lesions (p = 0.011). Based on a multivariate logistic regression analysis including 22 patients with TNBC also showed that a positive TLE3 expression significantly correlated with a better progression-free survival (p = 0.037). Conclusions: Our findings suggest that TLE3 is a useful marker for predicting the therapeutic effect of eribulin chemotherapy for TNBC. Disclosure: All authors have declared no conflicts of interest.
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