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

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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.


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.


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)


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.

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


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

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Correspondence to Risa Goto.

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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.

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Goto, R., Hirota, Y., Aruga, T. et al. The number of FoxP3-positive tumor-infiltrating lymphocytes in patients with synchronous bilateral breast cancer. Breast Cancer (2020).

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