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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2018

Open Access 01-12-2018 | Research

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

Authors: Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Katsuyuki Takahashi, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira

Published in: Journal of Translational Medicine | Issue 1/2018

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Abstract

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−, CFRlow and PDL1+ group (p = 0.045, log-rank) (p = 0.007, log-rank) (p = 0.040, log-rank), respectively. The CFRhigh group had significantly better OS than the CFRlow group (p = 0.034, log-rank). In the univariate analysis, CD8+, CFRhigh 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.
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Metadata
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
Authors
Koji Takada
Shinichiro Kashiwagi
Wataru Goto
Yuka Asano
Katsuyuki Takahashi
Tsutomu Takashima
Shuhei Tomita
Masahiko Ohsawa
Kosei Hirakawa
Masaichi Ohira
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-018-1460-4

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