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Study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment

BACKGROUND: Recently, the concepts of progression due to pre-existing lesions (PPL) and progression due to new metastasis (PNM) have been proposed to differentiate the progression types of treatment-resistant cancers. Previously, the differences between these two progression types did not affect the...

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Autores principales: Kashiwagi, Shinichiro, Tsujio, Gen, Asano, Yuka, Goto, Wataru, Takada, Koji, Takahashi, Katsuyuki, Morisaki, Tamami, Fujita, Hisakazu, Takashima, Tsutomu, Tomita, Shuhei, Ohsawa, Masahiko, Hirakawa, Kosei, Ohira, Masaichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845371/
https://www.ncbi.nlm.nih.gov/pubmed/29523158
http://dx.doi.org/10.1186/s12967-018-1443-5
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author Kashiwagi, Shinichiro
Tsujio, Gen
Asano, Yuka
Goto, Wataru
Takada, Koji
Takahashi, Katsuyuki
Morisaki, Tamami
Fujita, Hisakazu
Takashima, Tsutomu
Tomita, Shuhei
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
author_facet Kashiwagi, Shinichiro
Tsujio, Gen
Asano, Yuka
Goto, Wataru
Takada, Koji
Takahashi, Katsuyuki
Morisaki, Tamami
Fujita, Hisakazu
Takashima, Tsutomu
Tomita, Shuhei
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
author_sort Kashiwagi, Shinichiro
collection PubMed
description BACKGROUND: Recently, the concepts of progression due to pre-existing lesions (PPL) and progression due to new metastasis (PNM) have been proposed to differentiate the progression types of treatment-resistant cancers. Previously, the differences between these two progression types did not affect the determination of treatment strategies since both PPL and PNM are classified as progressive disease based on the response evaluation criteria in solid tumors (RECIST) diagnostic criteria. On the other hand, tumor infiltrating lymphocytes (TILs) are effective when used as indicators for monitoring the immune tumor microenvironment (iTME) in the cancer host, and TILs play an important role as biomarkers in predicting prognosis and therapeutic effects. This study focused on the progression types of cancer in patients undergoing eribulin chemotherapy. In addition, the iTME in individuals with PPL and PNM was evaluated using TILs as a marker. METHODS: Of the 52 patients with locally advanced or metastatic breast cancer who underwent chemotherapy with eribulin, 40 remained in the study, and 12 patients were dropout cases. The antitumor effect was evaluated based on the RECIST criteria using version 1.1. TILs were defined as the infiltrating lymphocytes within tumor stroma and were expressed in proportion to the field investigated. In PPL cases, the high-TIL group was considered as type I and the low-TIL group was classified as type II. In PNM cases, the high-TIL group was considered as type III and the low-TIL group was classified as type IV. RESULTS: In 19 cases, individuals with type I progression had significantly longer progression free survival and overall survival (OS) compared to those with type III progression (p = 0.040, p < 0.001, log-rank). Individuals with type I progression had significantly prolonged survival post progression compared to those with type II progression (p = 0.048, log-rank). A multivariate analysis that validate the effect of OS showed that these were independent factors of good prognosis (p = 0.003; hazard ratio [HR] = 0.065) (p = 0.006; HR = 0.105). CONCLUSIONS: The effects of eribulin chemotherapy suggested that patients with progressive-type breast cancer that proliferates in a good iTME may have a good prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1443-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-58453712018-03-19 Study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment Kashiwagi, Shinichiro Tsujio, Gen Asano, Yuka Goto, Wataru Takada, Koji Takahashi, Katsuyuki Morisaki, Tamami Fujita, Hisakazu Takashima, Tsutomu Tomita, Shuhei Ohsawa, Masahiko Hirakawa, Kosei Ohira, Masaichi J Transl Med Research BACKGROUND: Recently, the concepts of progression due to pre-existing lesions (PPL) and progression due to new metastasis (PNM) have been proposed to differentiate the progression types of treatment-resistant cancers. Previously, the differences between these two progression types did not affect the determination of treatment strategies since both PPL and PNM are classified as progressive disease based on the response evaluation criteria in solid tumors (RECIST) diagnostic criteria. On the other hand, tumor infiltrating lymphocytes (TILs) are effective when used as indicators for monitoring the immune tumor microenvironment (iTME) in the cancer host, and TILs play an important role as biomarkers in predicting prognosis and therapeutic effects. This study focused on the progression types of cancer in patients undergoing eribulin chemotherapy. In addition, the iTME in individuals with PPL and PNM was evaluated using TILs as a marker. METHODS: Of the 52 patients with locally advanced or metastatic breast cancer who underwent chemotherapy with eribulin, 40 remained in the study, and 12 patients were dropout cases. The antitumor effect was evaluated based on the RECIST criteria using version 1.1. TILs were defined as the infiltrating lymphocytes within tumor stroma and were expressed in proportion to the field investigated. In PPL cases, the high-TIL group was considered as type I and the low-TIL group was classified as type II. In PNM cases, the high-TIL group was considered as type III and the low-TIL group was classified as type IV. RESULTS: In 19 cases, individuals with type I progression had significantly longer progression free survival and overall survival (OS) compared to those with type III progression (p = 0.040, p < 0.001, log-rank). Individuals with type I progression had significantly prolonged survival post progression compared to those with type II progression (p = 0.048, log-rank). A multivariate analysis that validate the effect of OS showed that these were independent factors of good prognosis (p = 0.003; hazard ratio [HR] = 0.065) (p = 0.006; HR = 0.105). CONCLUSIONS: The effects of eribulin chemotherapy suggested that patients with progressive-type breast cancer that proliferates in a good iTME may have a good prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1443-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-09 /pmc/articles/PMC5845371/ /pubmed/29523158 http://dx.doi.org/10.1186/s12967-018-1443-5 Text en © The Author(s) 2018 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
Kashiwagi, Shinichiro
Tsujio, Gen
Asano, Yuka
Goto, Wataru
Takada, Koji
Takahashi, Katsuyuki
Morisaki, Tamami
Fujita, Hisakazu
Takashima, Tsutomu
Tomita, Shuhei
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
Study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment
title Study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment
title_full Study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment
title_fullStr Study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment
title_full_unstemmed Study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment
title_short Study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment
title_sort study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845371/
https://www.ncbi.nlm.nih.gov/pubmed/29523158
http://dx.doi.org/10.1186/s12967-018-1443-5
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