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Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression

BACKGROUND: “Avoiding immune destruction” has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study in...

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Autores principales: Asano, Yuka, Kashiwagi, Shinichiro, 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/PMC5883348/
https://www.ncbi.nlm.nih.gov/pubmed/29615063
http://dx.doi.org/10.1186/s12967-018-1458-y
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author Asano, Yuka
Kashiwagi, Shinichiro
Goto, Wataru
Takada, Koji
Takahashi, Katsuyuki
Morisaki, Tamami
Fujita, Hisakazu
Takashima, Tsutomu
Tomita, Shuhei
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
author_facet Asano, Yuka
Kashiwagi, Shinichiro
Goto, Wataru
Takada, Koji
Takahashi, Katsuyuki
Morisaki, Tamami
Fujita, Hisakazu
Takashima, Tsutomu
Tomita, Shuhei
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
author_sort Asano, Yuka
collection PubMed
description BACKGROUND: “Avoiding immune destruction” has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer. METHODS: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor, progesteron receptor, human epidermal growth factor receptor 2, Ki67, PD-L1, PDL-2 and PD-1 status were assessed by immunohistochemistry. RESULTS: There were 37 (20.9%) patients with high PD-1 expression, 42 (23.7%) patients had high PD-L1 expression, and 52 (29.4%) patients had high PD-L2 expression. The patients with high PD-1 and PD-L1 expressions had a significantly higher rate of triple-negative breast cancer (TNBC) (p = 0.041) (p < 0.001). In TNBC, patients with high PD-1 and PD-L1 expressions had significantly higher rates of non-pCR (p = 0.003) (p < 0.001). Univariate analysis showed that PD-1 and PD-L1 expressions also significantly shortened disease free survival in TNBC (p = 0.048, HR = 3.318) (p = 0.007, HR = 8.375). However, multivariate analysis found that only PD-L1 expression was an independent prognostic factor (p = 0.041, HR = 9.479). CONCLUSIONS: PD-1 and PD-L1 expressions may be useful as biomarkers to predict treatment responses to NAC in breast cancer. Above all, PD-L1 expression may also be useful as biomarkers for more effective chemotherapy in TNBC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1458-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-58833482018-04-10 Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression Asano, Yuka Kashiwagi, Shinichiro 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: “Avoiding immune destruction” has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer. METHODS: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor, progesteron receptor, human epidermal growth factor receptor 2, Ki67, PD-L1, PDL-2 and PD-1 status were assessed by immunohistochemistry. RESULTS: There were 37 (20.9%) patients with high PD-1 expression, 42 (23.7%) patients had high PD-L1 expression, and 52 (29.4%) patients had high PD-L2 expression. The patients with high PD-1 and PD-L1 expressions had a significantly higher rate of triple-negative breast cancer (TNBC) (p = 0.041) (p < 0.001). In TNBC, patients with high PD-1 and PD-L1 expressions had significantly higher rates of non-pCR (p = 0.003) (p < 0.001). Univariate analysis showed that PD-1 and PD-L1 expressions also significantly shortened disease free survival in TNBC (p = 0.048, HR = 3.318) (p = 0.007, HR = 8.375). However, multivariate analysis found that only PD-L1 expression was an independent prognostic factor (p = 0.041, HR = 9.479). CONCLUSIONS: PD-1 and PD-L1 expressions may be useful as biomarkers to predict treatment responses to NAC in breast cancer. Above all, PD-L1 expression may also be useful as biomarkers for more effective chemotherapy in TNBC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1458-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-04 /pmc/articles/PMC5883348/ /pubmed/29615063 http://dx.doi.org/10.1186/s12967-018-1458-y 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
Asano, Yuka
Kashiwagi, Shinichiro
Goto, Wataru
Takada, Koji
Takahashi, Katsuyuki
Morisaki, Tamami
Fujita, Hisakazu
Takashima, Tsutomu
Tomita, Shuhei
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression
title Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression
title_full Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression
title_fullStr Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression
title_full_unstemmed Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression
title_short Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression
title_sort prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883348/
https://www.ncbi.nlm.nih.gov/pubmed/29615063
http://dx.doi.org/10.1186/s12967-018-1458-y
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