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Predictive value of improvement in the immune tumour microenvironment in patients with breast cancer treated with neoadjuvant chemotherapy
  1. Wataru Goto1,
  2. Shinichiro Kashiwagi1,
  3. Yuka Asano1,
  4. Koji Takada1,
  5. Katsuyuki Takahashi2,
  6. Takaharu Hatano3,
  7. Tsutomu Takashima1,
  8. Shuhei Tomita2,
  9. Hisashi Motomura3,
  10. Masahiko Ohsawa4,
  11. Kosei Hirakawa1,
  12. Masaichi Ohira1
  1. 1Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
  2. 2Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan
  3. 3Department of Plastic and Reconstructive Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
  4. 4Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan
  1. Correspondence to Dr Shinichiro Kashiwagi; spqv9ke9{at}


Background Tumour-infiltrating lymphocytes (TILs) can be used to monitor the immune tumour microenvironment (iTME) and predict treatment response and outcome in breast cancer. We evaluated the prognostic significance of the levels of CD8+ TILs and forkhead box protein (FOXP3)-positive TILs before and after neoadjuvant chemotherapy (NAC).

Patients and methods We examined 136 patients with breast cancer treated with NAC. The number of CD8+ TILs and FOXP3+ TILs in biopsy specimens and residual tumours was evaluated by immunohistochemistry.

Results Patients with a high rate of change in the CD8/FOXP3 ratio (CFR) had significantly better recurrence-free survival (RFS) (p<0.001, log-rank). In multivariate analysis, the rates of change in the CD8+ TIL levels and the CFR were independent predictors for RFS (HR=2.304, p=0.036 and HR=4.663, p<0.001). In patients with triple-negative and hormone receptor-positive breast cancer, the rate of change in the CFR was an independent predictor for RFS (HR=13.021, p=0.002 and HR=4.377, p=0.003).

Conclusion Improvement in the iTME following NAC is correlated with good outcome. The rate of change in the CFR may be a useful biomarker to predict prognosis of patients treated with NAC.

  • tumour microenvironment
  • breast cancer
  • immune response
  • neoadjuvant chemotherapy
  • tumour-infiltrating lymphocytes

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  • Contributors All authors were involved in the preparation of the manuscript. WG collected the data and wrote the manuscript. SK, YA, KTakad, KTakah, TH and TT performed the operation and designed the study. WG, SK and ST summarised the data and revised the manuscript. MOhs performed the pathological diagnosis. HM, KH and MOhi made substantial contribution to the study design, performed the operation and revised the manuscript. All authors read and approved the final manuscript.

  • Funding This study was supported in part by Grants-in Aid for Scientific Research (KAKENHI, nos 25461992, 26461957 and 17K10559) from the Ministry of Education, Science, Sports, Culture and Technology of Japan.

  • Competing interests Not declared.

  • Patient consent Obtained.

  • Ethics approval The Ethics Committee of Osaka City University approved the study protocol (no 926).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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