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Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer

BACKGROUND: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in pr...

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Autores principales: Takada, Koji, Kashiwagi, Shinichiro, Goto, Wataru, Asano, Yuka, Takahashi, Katsuyuki, 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/PMC5883877/
https://www.ncbi.nlm.nih.gov/pubmed/29615076
http://dx.doi.org/10.1186/s12967-018-1460-4
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author Takada, Koji
Kashiwagi, Shinichiro
Goto, Wataru
Asano, Yuka
Takahashi, Katsuyuki
Takashima, Tsutomu
Tomita, Shuhei
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
author_facet Takada, Koji
Kashiwagi, Shinichiro
Goto, Wataru
Asano, Yuka
Takahashi, Katsuyuki
Takashima, Tsutomu
Tomita, Shuhei
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
author_sort Takada, Koji
collection PubMed
description BACKGROUND: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators. METHODS: The subjects consisted of 30 patients who received the TPD regimen. The expression levels of estrogen receptor, progesterone receptor, Ki67, CD8, forkhead box protein (FOXP) 3, programmed death (PD) 1, programmed death ligand (PD-L) 1, CD163, phosphatase and tensin homolog and lymphocyte activation gene 3 were evaluated in biopsy specimens, by immunostaining. RESULTS: CD8(+), CD8/FOXP3 ratio (CFR)(high) and PD-L1(−) group had significantly longer PFS than the CD8(−), CFR(low) and PDL1(+) group (p = 0.045, log-rank) (p = 0.007, log-rank) (p = 0.040, log-rank), respectively. The CFR(high) group had significantly better OS than the CFR(low) group (p = 0.034, log-rank). In the univariate analysis, CD8(+), CFR(high) groups extended PFS significantly (p = 0.027, hazard ratio [HR] = 0.162) (p = 0.008, HR = 0.195), respectively. The receiver operating characteristic (ROC) analyses showed that the results for CFR [area under the curve (AUC): 0.708] were better than those for other factors (AUC: CD8 = 0.681, FOXP3 = 0.639, PD1 = 0.528, PD-L1 = 0.681). CONCLUSIONS: This study shows with the TPD regimen, a high CFR leads to a high ORR and long PFS in HER2-positive breast cancer. CFR, therefore, may be one of the important prognostic factors for this disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1460-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-58838772018-04-09 Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer Takada, Koji Kashiwagi, Shinichiro Goto, Wataru Asano, Yuka Takahashi, Katsuyuki Takashima, Tsutomu Tomita, Shuhei Ohsawa, Masahiko Hirakawa, Kosei Ohira, Masaichi J Transl Med Research BACKGROUND: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators. METHODS: The subjects consisted of 30 patients who received the TPD regimen. The expression levels of estrogen receptor, progesterone receptor, Ki67, CD8, forkhead box protein (FOXP) 3, programmed death (PD) 1, programmed death ligand (PD-L) 1, CD163, phosphatase and tensin homolog and lymphocyte activation gene 3 were evaluated in biopsy specimens, by immunostaining. RESULTS: CD8(+), CD8/FOXP3 ratio (CFR)(high) and PD-L1(−) group had significantly longer PFS than the CD8(−), CFR(low) and PDL1(+) group (p = 0.045, log-rank) (p = 0.007, log-rank) (p = 0.040, log-rank), respectively. The CFR(high) group had significantly better OS than the CFR(low) group (p = 0.034, log-rank). In the univariate analysis, CD8(+), CFR(high) groups extended PFS significantly (p = 0.027, hazard ratio [HR] = 0.162) (p = 0.008, HR = 0.195), respectively. The receiver operating characteristic (ROC) analyses showed that the results for CFR [area under the curve (AUC): 0.708] were better than those for other factors (AUC: CD8 = 0.681, FOXP3 = 0.639, PD1 = 0.528, PD-L1 = 0.681). CONCLUSIONS: This study shows with the TPD regimen, a high CFR leads to a high ORR and long PFS in HER2-positive breast cancer. CFR, therefore, may be one of the important prognostic factors for this disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1460-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-03 /pmc/articles/PMC5883877/ /pubmed/29615076 http://dx.doi.org/10.1186/s12967-018-1460-4 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
Takada, Koji
Kashiwagi, Shinichiro
Goto, Wataru
Asano, Yuka
Takahashi, Katsuyuki
Takashima, Tsutomu
Tomita, Shuhei
Ohsawa, Masahiko
Hirakawa, Kosei
Ohira, Masaichi
Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer
title Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer
title_full Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer
title_fullStr Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer
title_full_unstemmed Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer
title_short Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer
title_sort use of the tumor-infiltrating cd8 to foxp3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced her2-positive breast cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883877/
https://www.ncbi.nlm.nih.gov/pubmed/29615076
http://dx.doi.org/10.1186/s12967-018-1460-4
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