An increase in tumor-infiltrating lymphocytes after treatment is significantly associated with a poor response to neoadjuvant endocrine therapy for estrogen receptor-positive/HER2-negative breast cancers
Background The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)− breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy...
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Published in | Breast cancer (Tokyo, Japan) Vol. 30; no. 5; pp. 703 - 713 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Singapore
Springer Nature Singapore
01.09.2023
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Subjects | |
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Abstract | Background
The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)− breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy (NET) was examined.
Methods
We recruited 170 patients with ER + /HER2− breast cancer who were treated with preoperative endocrine monotherapy. TILs were evaluated before and after NET, and their changes were noted. Furthermore, T cell subtypes were examined using CD8 and FOXP3 immunohistochemical analyses. Neutrophil and lymphocyte counts in the peripheral blood were analyzed with reference to TIL levels or changes. Responders were defined as Ki67 expression levels ≤ 2.7% after treatment.
Results
Post-treatment (
p
= 0.016), but not pre-treatment (
p
= 0.464), TIL levels were significantly associated with the response to NET. TIL levels increased significantly after treatment among non-responders (
p
= 0.001). FOXP3 + T cell counts increased significantly after treatment in patients with increased TILs (
p
= 0.035), but not in those without increased TILs (
p
= 0.281). Neutrophil counts decreased significantly after treatment in patients without increased TILs (
p
= 0.026), but not in patients with increased TILs (
p
= 0.312).
Conclusion
An increase in TILs after NET was significantly associated with a poor response to NET. Given that FOXP3 + T-cell counts increased, and neutrophil counts did not decrease in patients with increased TILs after NET, the induction of an immunosuppressive microenvironment was speculated to play a role in the inferior efficacy. These data might partially indicate the involvement of the immune response in the efficacy of endocrine therapy. |
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AbstractList | The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)- breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy (NET) was examined.
We recruited 170 patients with ER + /HER2- breast cancer who were treated with preoperative endocrine monotherapy. TILs were evaluated before and after NET, and their changes were noted. Furthermore, T cell subtypes were examined using CD8 and FOXP3 immunohistochemical analyses. Neutrophil and lymphocyte counts in the peripheral blood were analyzed with reference to TIL levels or changes. Responders were defined as Ki67 expression levels ≤ 2.7% after treatment.
Post-treatment (p = 0.016), but not pre-treatment (p = 0.464), TIL levels were significantly associated with the response to NET. TIL levels increased significantly after treatment among non-responders (p = 0.001). FOXP3 + T cell counts increased significantly after treatment in patients with increased TILs (p = 0.035), but not in those without increased TILs (p = 0.281). Neutrophil counts decreased significantly after treatment in patients without increased TILs (p = 0.026), but not in patients with increased TILs (p = 0.312).
An increase in TILs after NET was significantly associated with a poor response to NET. Given that FOXP3 + T-cell counts increased, and neutrophil counts did not decrease in patients with increased TILs after NET, the induction of an immunosuppressive microenvironment was speculated to play a role in the inferior efficacy. These data might partially indicate the involvement of the immune response in the efficacy of endocrine therapy. BACKGROUNDThe reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)- breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy (NET) was examined.METHODSWe recruited 170 patients with ER + /HER2- breast cancer who were treated with preoperative endocrine monotherapy. TILs were evaluated before and after NET, and their changes were noted. Furthermore, T cell subtypes were examined using CD8 and FOXP3 immunohistochemical analyses. Neutrophil and lymphocyte counts in the peripheral blood were analyzed with reference to TIL levels or changes. Responders were defined as Ki67 expression levels ≤ 2.7% after treatment.RESULTSPost-treatment (p = 0.016), but not pre-treatment (p = 0.464), TIL levels were significantly associated with the response to NET. TIL levels increased significantly after treatment among non-responders (p = 0.001). FOXP3 + T cell counts increased significantly after treatment in patients with increased TILs (p = 0.035), but not in those without increased TILs (p = 0.281). Neutrophil counts decreased significantly after treatment in patients without increased TILs (p = 0.026), but not in patients with increased TILs (p = 0.312).CONCLUSIONAn increase in TILs after NET was significantly associated with a poor response to NET. Given that FOXP3 + T-cell counts increased, and neutrophil counts did not decrease in patients with increased TILs after NET, the induction of an immunosuppressive microenvironment was speculated to play a role in the inferior efficacy. These data might partially indicate the involvement of the immune response in the efficacy of endocrine therapy. Abstract Background The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)− breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy (NET) was examined. Methods We recruited 170 patients with ER + /HER2− breast cancer who were treated with preoperative endocrine monotherapy. TILs were evaluated before and after NET, and their changes were noted. Furthermore, T cell subtypes were examined using CD8 and FOXP3 immunohistochemical analyses. Neutrophil and lymphocyte counts in the peripheral blood were analyzed with reference to TIL levels or changes. Responders were defined as Ki67 expression levels ≤ 2.7% after treatment. Results Post-treatment ( p = 0.016), but not pre-treatment ( p = 0.464), TIL levels were significantly associated with the response to NET. TIL levels increased significantly after treatment among non-responders ( p = 0.001). FOXP3 + T cell counts increased significantly after treatment in patients with increased TILs ( p = 0.035), but not in those without increased TILs ( p = 0.281). Neutrophil counts decreased significantly after treatment in patients without increased TILs ( p = 0.026), but not in patients with increased TILs ( p = 0.312). Conclusion An increase in TILs after NET was significantly associated with a poor response to NET. Given that FOXP3 + T-cell counts increased, and neutrophil counts did not decrease in patients with increased TILs after NET, the induction of an immunosuppressive microenvironment was speculated to play a role in the inferior efficacy. These data might partially indicate the involvement of the immune response in the efficacy of endocrine therapy. Background The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)− breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy (NET) was examined. Methods We recruited 170 patients with ER + /HER2− breast cancer who were treated with preoperative endocrine monotherapy. TILs were evaluated before and after NET, and their changes were noted. Furthermore, T cell subtypes were examined using CD8 and FOXP3 immunohistochemical analyses. Neutrophil and lymphocyte counts in the peripheral blood were analyzed with reference to TIL levels or changes. Responders were defined as Ki67 expression levels ≤ 2.7% after treatment. Results Post-treatment ( p = 0.016), but not pre-treatment ( p = 0.464), TIL levels were significantly associated with the response to NET. TIL levels increased significantly after treatment among non-responders ( p = 0.001). FOXP3 + T cell counts increased significantly after treatment in patients with increased TILs ( p = 0.035), but not in those without increased TILs ( p = 0.281). Neutrophil counts decreased significantly after treatment in patients without increased TILs ( p = 0.026), but not in patients with increased TILs ( p = 0.312). Conclusion An increase in TILs after NET was significantly associated with a poor response to NET. Given that FOXP3 + T-cell counts increased, and neutrophil counts did not decrease in patients with increased TILs after NET, the induction of an immunosuppressive microenvironment was speculated to play a role in the inferior efficacy. These data might partially indicate the involvement of the immune response in the efficacy of endocrine therapy. |
Author | Hirota, Seiichi Miyoshi, Yasuo Watanabe, Takahiro Ishikawa, Eri Morimoto, Koji Fukui, Reiko Fujimoto, Yukie Nagahashi, Masayuki |
Author_xml | – sequence: 1 givenname: Reiko surname: Fukui fullname: Fukui, Reiko organization: Department of Surgery, Division of Breast and Endocrine Surgery, School of Medicine, Hyogo Medical University – sequence: 2 givenname: Takahiro surname: Watanabe fullname: Watanabe, Takahiro organization: Department of Clinical Pathology, Chibune General Hospital – sequence: 3 givenname: Koji surname: Morimoto fullname: Morimoto, Koji organization: Department of Nutrition, College of Nutrition, Koshien University – sequence: 4 givenname: Yukie surname: Fujimoto fullname: Fujimoto, Yukie organization: Department of Surgery, Division of Breast and Endocrine Surgery, School of Medicine, Hyogo Medical University – sequence: 5 givenname: Masayuki surname: Nagahashi fullname: Nagahashi, Masayuki organization: Department of Surgery, Division of Breast and Endocrine Surgery, School of Medicine, Hyogo Medical University – sequence: 6 givenname: Eri surname: Ishikawa fullname: Ishikawa, Eri organization: Department of Surgical Pathology, School of Medicine, Hyogo Medical University – sequence: 7 givenname: Seiichi surname: Hirota fullname: Hirota, Seiichi organization: Department of Surgical Pathology, School of Medicine, Hyogo Medical University – sequence: 8 givenname: Yasuo orcidid: 0000-0001-8535-4008 surname: Miyoshi fullname: Miyoshi, Yasuo email: ymiyoshi@hyo-med.ac.jp organization: Department of Surgery, Division of Breast and Endocrine Surgery, School of Medicine, Hyogo Medical University |
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Keywords | Endocrine therapy Breast cancer Tumor-infiltrating lymphocytes FOXP3 CD8 |
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The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)− breast cancer patients with high... The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)- breast cancer patients with high levels of... Abstract Background The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)− breast cancer patients with... BACKGROUNDThe reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)- breast cancer patients with high... |
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Title | An increase in tumor-infiltrating lymphocytes after treatment is significantly associated with a poor response to neoadjuvant endocrine therapy for estrogen receptor-positive/HER2-negative breast cancers |
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