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Open Access 01-07-2020 | Breast Cancer | Original Article

Influences of preoperative metformin on immunological factors in early breast cancer

Authors: Takahiro Tsukioki, Tadahiko Shien, Takehiro Tanaka, Yoko Suzuki, Yukiko Kajihara, Minami Hatono, Kengo Kawada, Mariko Kochi, Takayuki Iwamoto, Hirokuni Ikeda, Naruto Taira, Hiroyoshi Doihara, Shinichi Toyooka

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2020

Abstract

Purpose

Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer.

Method

We evaluated the effects on immunological factors (TILs, CD4 + , CD8 + , PD-L1, IFNγ and IL-2) by comparing core needle biopsies (CNB) obtained before metformin treatment with surgical specimens. Seventeen patients were enrolled in this prospective study from January to December 2016. We also analyzed 59 patients undergoing surgery during the same period to reveal the correlation of immune factors between CNB and surgical specimen.

Result

There was a moderate correlation between CNB and surgical specimens on TILs and CD8 + lymphocyte. (TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%). The expressions of CD4 + and CD8 + by TILs were increased in 41% and 18% of surgical specimens, respectively. However, TILs number (p = 0.0554), CD4+ (p = 0.0613) and CD8 + (p = 0.0646) expressions did not significantly increased. Furthermore, IFNγ expression appeared to be increased in response to metformin (p = 0.08).

Conclusion

Preoperative metformin tends to increase TILs, as well as the numbers of CD4 and CD8 positive lymphocytes, and IFNγ levels. Metformin might improve immune function and have a possibility of chemo-sensitivity and thereby increase the effectiveness of immunotherapy, based on the results of this preliminary study.

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Title: Influences of preoperative metformin on immunological factors in early breast cancer
Authors: Takahiro Tsukioki
Tadahiko Shien
Takehiro Tanaka
Yoko Suzuki
Yukiko Kajihara
Minami Hatono
Kengo Kawada
Mariko Kochi
Takayuki Iwamoto
Hirokuni Ikeda
Naruto Taira
Hiroyoshi Doihara
Shinichi Toyooka
Publication date: 01-07-2020
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Metformin
Breast Cancer
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04092-2

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