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Research ArticleClinical Studies

Outcome Prediction After Neoadjuvant Chemotherapy (NAC) for Breast Cancer, Using Tumor-infiltrating Lymphocytes Within Fibrotic Foci of Tumor Stroma (FF-TILs)

SHINICHIRO KASHIWAGI, YUKA ASANO, KOJI TAKADA, WATARU GOTO, TAMAMI MORISAKI, MASATSUNE SHIBUTANI, HIROAKI TANAKA, KOSEI HIRAKAWA and MASAICHI OHIRA
Anticancer Research March 2022, 42 (3) 1421-1431; DOI: https://doi.org/10.21873/anticanres.15612
SHINICHIRO KASHIWAGI
1Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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  • For correspondence: kashiwa@med.osaka-cu.ac.jp
YUKA ASANO
1Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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KOJI TAKADA
1Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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WATARU GOTO
1Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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TAMAMI MORISAKI
1Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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MASATSUNE SHIBUTANI
2Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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HIROAKI TANAKA
2Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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KOSEI HIRAKAWA
1Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
2Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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MASAICHI OHIRA
1Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
2Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Abstract

Background/Aim: Tumor-infiltrating lymphocytes (TILs), which are indicators of immune response monitoring, are generally mononuclear immunocytes that aggregate with tumors and are thought to have a close relationship with cancer cells. On the other hand, a fibrotic focus (FF) within the stroma of a tumor is a histological formation that plays an important role in the cancer microenvironment with regard to proliferation and development. Here, we focused on TILs that exist within the FF and performed pathological evaluations. Patients and Methods: Of the 320 patients treated with neoadjuvant chemotherapy (NAC), 239 subjects who were able to evaluate FF-TILs were targeted. Lymphocytes that infiltrate the FF are FF-TILs. Results: The disease-free survival (DFS) period after NAC for the high-FF-TIL group was found to be significantly longer than that for the low-FF-TIL group for all cases (p<0.001) and for all subtypes of triple-negative breast cancer (TNBC) (p=0.001), human epidermal growth factor receptor 2-enriched breast cancer (HER2BC) (p=0.010), and hormone receptor-positive breast cancer (HRBC) (p=0.003). In multivariable analysis as well, high-FF-TIL group classification was an independent factor for recurrence after NAC for all cases [p<0.001, hazard ratio (HR)=0.198] and all subtypes of TNBC (p=0.006, HR=0.172), HER2BC (p=0.025, HR=0.135), and HRBC (p=0.007, HR=0.228). Conclusion: FF-TILs are possibly a useful factor for predicting recurrence of breast cancer after NAC.

Key Words:
  • Tumor-infiltrating lymphocytes
  • neoadjuvant chemotherapy
  • breast cancer
  • fibrotic foci
  • prognostic marker
  • Received January 18, 2022.
  • Revision received February 5, 2022.
  • Accepted February 7, 2022.
  • Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 42 (3)
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Outcome Prediction After Neoadjuvant Chemotherapy (NAC) for Breast Cancer, Using Tumor-infiltrating Lymphocytes Within Fibrotic Foci of Tumor Stroma (FF-TILs)
SHINICHIRO KASHIWAGI, YUKA ASANO, KOJI TAKADA, WATARU GOTO, TAMAMI MORISAKI, MASATSUNE SHIBUTANI, HIROAKI TANAKA, KOSEI HIRAKAWA, MASAICHI OHIRA
Anticancer Research Mar 2022, 42 (3) 1421-1431; DOI: 10.21873/anticanres.15612

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Outcome Prediction After Neoadjuvant Chemotherapy (NAC) for Breast Cancer, Using Tumor-infiltrating Lymphocytes Within Fibrotic Foci of Tumor Stroma (FF-TILs)
SHINICHIRO KASHIWAGI, YUKA ASANO, KOJI TAKADA, WATARU GOTO, TAMAMI MORISAKI, MASATSUNE SHIBUTANI, HIROAKI TANAKA, KOSEI HIRAKAWA, MASAICHI OHIRA
Anticancer Research Mar 2022, 42 (3) 1421-1431; DOI: 10.21873/anticanres.15612
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Keywords

  • tumor-infiltrating lymphocytes
  • neoadjuvant chemotherapy
  • Breast cancer
  • fibrotic foci
  • prognostic marker
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