Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression
"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 inve...
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Published in | Journal of translational medicine Vol. 16; no. 1; p. 87 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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England
BioMed Central Ltd
04.04.2018
BioMed Central BMC |
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Abstract | "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.
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.
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).
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. |
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AbstractList | "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.
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.
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).
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. Abstract 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. 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.METHODSA 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.RESULTSThere 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).CONCLUSIONSPD-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. 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. Keywords: Immune checkpoint, Triple-negative breast cancer, Pathological complete response, Neoadjuvant chemotherapy, PD-1, PD-L1 "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. 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. 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). 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. |
ArticleNumber | 87 |
Audience | Academic |
Author | Asano, Yuka Fujita, Hisakazu Takada, Koji Ohira, Masaichi Takashima, Tsutomu Hirakawa, Kosei Kashiwagi, Shinichiro Takahashi, Katsuyuki Tomita, Shuhei Goto, Wataru Ohsawa, Masahiko Morisaki, Tamami |
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Keywords | Neoadjuvant chemotherapy PD-L1 Pathological complete response Immune checkpoint PD-1 Triple-negative breast cancer |
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Snippet | "Avoiding immune destruction" has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand... Background "Avoiding immune destruction" has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell... BACKGROUND"Avoiding immune destruction" has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell... Abstract Background “Avoiding immune destruction” has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed... |
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SubjectTerms | Adjuvant chemotherapy Breast cancer Chemotherapy, Adjuvant Disease-Free Survival Drug therapy Gene expression Genetic aspects Humans Immune checkpoint Middle Aged Multivariate Analysis Neoadjuvant chemotherapy Neoadjuvant Therapy Neoplasm Proteins - metabolism Pathological complete response Patient outcomes PD-1 PD-L1 Physiological aspects Treatment Outcome Triple Negative Breast Neoplasms - drug therapy Triple Negative Breast Neoplasms - immunology Triple-negative breast cancer |
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Title | Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression |
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