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Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study

BACKGROUND: Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies. However, the development of CTCs as a predictive marker for treatment effects on breast cancer remains an enormous task. We investigated CTCs, including...

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Autores principales: Horimoto, Yoshiya, Tokuda, Emi, Murakami, Fumi, Uomori, Toshitaka, Himuro, Takanori, Nakai, Katsuya, Orihata, Gotaro, Iijima, Kotaro, Togo, Shinsaku, Shimizu, Hideo, Saito, Mitsue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195982/
https://www.ncbi.nlm.nih.gov/pubmed/30342534
http://dx.doi.org/10.1186/s12967-018-1663-8
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author Horimoto, Yoshiya
Tokuda, Emi
Murakami, Fumi
Uomori, Toshitaka
Himuro, Takanori
Nakai, Katsuya
Orihata, Gotaro
Iijima, Kotaro
Togo, Shinsaku
Shimizu, Hideo
Saito, Mitsue
author_facet Horimoto, Yoshiya
Tokuda, Emi
Murakami, Fumi
Uomori, Toshitaka
Himuro, Takanori
Nakai, Katsuya
Orihata, Gotaro
Iijima, Kotaro
Togo, Shinsaku
Shimizu, Hideo
Saito, Mitsue
author_sort Horimoto, Yoshiya
collection PubMed
description BACKGROUND: Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies. However, the development of CTCs as a predictive marker for treatment effects on breast cancer remains an enormous task. We investigated CTCs, including epithelial mesenchymal transition (EMT) status, from metastatic breast cancer patients who had received eribulin-based treatment, which reportedly suppresses EMT as a means of tumour suppression. Our aim was to test the possibility of this method serving as a tool predicting eribulin efficacy. METHODS: Twenty-two patients were enrolled and peripheral blood samples were collected before eribulin treatment. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Progression-free survival (PFS) and clinical response were assessable in 20 and 18 patients, respectively, in relation to the number of CTCs. RESULTS: Numbers of total CTCs were significantly increased in patients with progressive disease during treatment (p = 0.006). Median PFS was 14.6 weeks and patients with more total and mesenchymal CTCs at baseline had significantly shorter PFS (p = 0.0013 and 0.013, respectively). Multivariate logistic regression analysis revealed small number of total baseline CTCs and long disease-free survival to be related to long PFS (p = 0.0004 and 0.020, respectively). CONCLUSIONS: Our data suggest that determining both mesenchymal and epithelial CTCs at baseline might be a good tool for predicting eribulin responsiveness. Evaluation of mesenchymal CTC can be considered as a parameter in larger studies, while most clinical trials are currently employing only the detection of the epithelial cellular adhesion molecule (EpCAM). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1663-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-61959822018-10-30 Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study Horimoto, Yoshiya Tokuda, Emi Murakami, Fumi Uomori, Toshitaka Himuro, Takanori Nakai, Katsuya Orihata, Gotaro Iijima, Kotaro Togo, Shinsaku Shimizu, Hideo Saito, Mitsue J Transl Med Research BACKGROUND: Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies. However, the development of CTCs as a predictive marker for treatment effects on breast cancer remains an enormous task. We investigated CTCs, including epithelial mesenchymal transition (EMT) status, from metastatic breast cancer patients who had received eribulin-based treatment, which reportedly suppresses EMT as a means of tumour suppression. Our aim was to test the possibility of this method serving as a tool predicting eribulin efficacy. METHODS: Twenty-two patients were enrolled and peripheral blood samples were collected before eribulin treatment. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Progression-free survival (PFS) and clinical response were assessable in 20 and 18 patients, respectively, in relation to the number of CTCs. RESULTS: Numbers of total CTCs were significantly increased in patients with progressive disease during treatment (p = 0.006). Median PFS was 14.6 weeks and patients with more total and mesenchymal CTCs at baseline had significantly shorter PFS (p = 0.0013 and 0.013, respectively). Multivariate logistic regression analysis revealed small number of total baseline CTCs and long disease-free survival to be related to long PFS (p = 0.0004 and 0.020, respectively). CONCLUSIONS: Our data suggest that determining both mesenchymal and epithelial CTCs at baseline might be a good tool for predicting eribulin responsiveness. Evaluation of mesenchymal CTC can be considered as a parameter in larger studies, while most clinical trials are currently employing only the detection of the epithelial cellular adhesion molecule (EpCAM). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1663-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-20 /pmc/articles/PMC6195982/ /pubmed/30342534 http://dx.doi.org/10.1186/s12967-018-1663-8 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
Horimoto, Yoshiya
Tokuda, Emi
Murakami, Fumi
Uomori, Toshitaka
Himuro, Takanori
Nakai, Katsuya
Orihata, Gotaro
Iijima, Kotaro
Togo, Shinsaku
Shimizu, Hideo
Saito, Mitsue
Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study
title Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study
title_full Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study
title_fullStr Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study
title_full_unstemmed Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study
title_short Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study
title_sort analysis of circulating tumour cell and the epithelial mesenchymal transition (emt) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195982/
https://www.ncbi.nlm.nih.gov/pubmed/30342534
http://dx.doi.org/10.1186/s12967-018-1663-8
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