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Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer

BACKGROUND: The recently developed reagent, eribulin mesylate (eribulin), is a microtubule dynamics inhibitor with a mechanism of action that differs from those of taxanes and vinca alkaloids. This drug is considered to be a promising chemotherapeutic agent for the treatment of locally advanced or m...

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Detalles Bibliográficos
Autores principales: Kashiwagi, Shinichiro, Fukushima, Wakaba, Asano, Yuka, Goto, Wataru, Takada, Koji, Noda, Satoru, Takashima, Tsutomu, Onoda, Naoyoshi, Ohsawa, Masahiko, Hirakawa, Kosei, Ohira, Masaichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580315/
https://www.ncbi.nlm.nih.gov/pubmed/28859615
http://dx.doi.org/10.1186/s12885-017-3598-5
Descripción
Sumario:BACKGROUND: The recently developed reagent, eribulin mesylate (eribulin), is a microtubule dynamics inhibitor with a mechanism of action that differs from those 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 if variables such as tumor expression of β-tubulin class III, glutathione S-transferase pi (GSTP) 1 or transducin-like enhancer of split (TLE) 3 might act as predictive factors on the therapeutic effect of eribulin chemotherapy. METHODS: The subjects included 52 patients with MBC who underwent chemotherapy with eribulin. The expression levels of Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor (HER) 2, Ki67, β-tubulin class III, GSTP-1 and TLE-3 were evaluated using immunostaining employing needle biopsy specimens. RESULTS: Patients with TLE3-negative tumors displayed significantly poorer outcomes regarding progression-free survival than patients with TLE3-positive tumors when prognosis within the group of patients with triple-negative breast cancer (TNBC) lesions was analyzed (p = 0.011, log-rank). In contrast, no such difference in prognosis was found in a comparison of TLE-3 positive/negative patients in the group of all patients (p = 0.433, log-rank) or of patients with non-TNBC lesions (p = 0.659, log-rank). Based on a univariate analysis of 22 TNBC cases, a better progression-free survival correlated significantly with a positive TLE3 expression in the tumor (p = 0.025). 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3598-5) contains supplementary material, which is available to authorized users.