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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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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
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author Kashiwagi, Shinichiro
Fukushima, Wakaba
Asano, Yuka
Goto, Wataru
Takada, Koji
Noda, Satoru
Takashima, Tsutomu
Onoda, Naoyoshi
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
author_facet Kashiwagi, Shinichiro
Fukushima, Wakaba
Asano, Yuka
Goto, Wataru
Takada, Koji
Noda, Satoru
Takashima, Tsutomu
Onoda, Naoyoshi
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
author_sort Kashiwagi, Shinichiro
collection PubMed
description 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.
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spelling pubmed-55803152017-09-07 Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer Kashiwagi, Shinichiro Fukushima, Wakaba Asano, Yuka Goto, Wataru Takada, Koji Noda, Satoru Takashima, Tsutomu Onoda, Naoyoshi Ohsawa, Masahiko Hirakawa, Kosei Ohira, Masaichi BMC Cancer Research Article 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. BioMed Central 2017-08-31 /pmc/articles/PMC5580315/ /pubmed/28859615 http://dx.doi.org/10.1186/s12885-017-3598-5 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kashiwagi, Shinichiro
Fukushima, Wakaba
Asano, Yuka
Goto, Wataru
Takada, Koji
Noda, Satoru
Takashima, Tsutomu
Onoda, Naoyoshi
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer
title Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer
title_full Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer
title_fullStr Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer
title_full_unstemmed Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer
title_short Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer
title_sort identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer
topic Research Article
url 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
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