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The number of FoxP3-positive tumor-infiltrating lymphocytes in patients with synchronous bilateral breast cancer

  • Risa GotoEmail author
  • Yuko Hirota
  • Tomoyuki Aruga
  • Shinichiro Horiguchi
  • Sakiko Miura
  • Seigo Nakamura
  • Masafumi Takimoto
Original Article
  • 14 Downloads

Abstract

Purpose

In breast cancer, FoxP3-positive tumor-infiltrating lymphocytes (FoxP3+ TILs) vary depending on lymph node status, histological grade, and subtype. All these studies have compared the numbers of FoxP3+ TILs among different hosts, but recruitment of FoxP3+ TILs might depend on each individual’s immune environment and each tumor’s biological characteristics. In the present study, FoxP3+ TIL numbers were investigated in patients with synchronous bilateral breast cancer (SBBC) to determine the factors that affect FoxP3+ TIL recruitment in the same anti-tumor immune environment.

Methods

Patients diagnosed with SBBC who underwent curative surgery at two institutions were enrolled in this study. Patients who underwent primary systemic therapy or who were diagnosed with ductal carcinoma in situ or who had distant metastases at diagnosis were excluded. The average numbers of Foxp3+ TILs were determined from the scores of five high-power microscopic fields (HPF). The associations between Foxp3+ TIL numbers and the clinicopathological features of bilateral breasts in a single individual were examined.

Results

Nuclear grade (NG) (p = 0.007) and subtype (p = 0.03), but not size (p = 0.18) and axillary lymph node (p = 0.23) were significantly associated with increase of FoxP3 + TIL numbers by univariate analysis. Further, only NG was a statistically significant clinicopathological factor for change in the number of FoxP3+ TILs by multivariate analysis (p = 0.046)

Conclusions

There was no relationship between FoxP3+ TIL numbers and cancer progression as reflected in tumor size and axillary lymph node in patients with SBBC. Aggressive biological factors, especially high NG, were significantly related to enhanced recruitment of FoxP3+ TILs.

Keywords

Synchronous bilateral breast cancer Tumor-infiltrating lymphocytes FoxP3 Regulatory T cell Anti-tumor immunity environment 

Notes

Acknowledgements

We thank Ms. Tomoko Nagai, medical technician of department of pathology Showa University School of Medicine, for technical assistance with immunostaining method.

Funding

The present study was supported by Clinical Research Found of Tokyo Metropolitan Government (Grant no. H290303015).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the ethics committee of Showa University Hospital (approval number #1969), and Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital (approval number #1638).

Informed consent

Participants comprehensively provided their consent stating that the tissue samples from resected specimen may be used for various researches. The ethics committee of Showa University Hospital (approval number #1969), and Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital (approval number #1638) approved the authors’ request for waiver of informed consent based on ethical consideration. All patients have the option to confirm ongoing studies on Showa University and Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital web sites and may choose to opt out of consent at any time. The ethics committee approved this consent procedure.

Supplementary material

12282_2020_1049_MOESM1_ESM.tif (1.9 mb)
Supplementary Fig. 1 Flow diagram describe patient’s inclusion in present study file1 (TIF 1963 kb)
12282_2020_1049_MOESM2_ESM.tif (4.9 mb)
Supplementary Fig. 2 The median of FoxP3-positive tumor-infiltrating lymphocytes (FoxP3+ TILs) increased in order from luminal type with nuclear grade (NG) 1/2, luminal type with NG3, HER2 type, to basal-type (TIF 5000 kb)

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Copyright information

© The Japanese Breast Cancer Society 2020

Authors and Affiliations

  1. 1.Department of Breast Surgical OncologyTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  2. 2.Department of PathologyShowa UniversityTokyoJapan
  3. 3.Department of PathologyShowa University Koto Toyosu HospitalTokyoJapan
  4. 4.Department of PathologyTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  5. 5.Department of Surgery, Division of Breast Surgical OncologyShowa UniversityTokyoJapan

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