Breast Cancer, Diabetes Mellitus and Glucagon-Like Peptide-1 Receptor Toward Exploring Their Possible Associations

Naoko Hashimoto Takigami, Shimpei Kuniyoshi, Yasuhiro Miki, Kentaro Tamaki, Yoshihiko Kamada, Kano Uehara, Seiko Tsuchiya, Shigeharu Terukina, Erina Iwabuchi, Ayako Kanai, Minoru Miyashita, Takanori Ishida, Nobumitsu Tamaki, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Diabetes Mellitus (DM) has been one of the well known risk factors of breast cancer (BC) development and also associated with adverse clinical outcomes of BC patients. Glucagon-like peptide-1 (GLP-1) receptor agonists have been used as antidiabetic therapeutic agents and recent epidemiological studies have reported their use to be correlated with increased BC risks. However, biological or pathological details have remained unknown. Therefore, in this study, we examined the status of GLP-1 receptor (GLP-1R) in BC with and without DM and correlated the findings with the clinicopathological factors of the patients to explore the possible involvement of GLP-1 in BC pathology. Methods: We immunolocalized GLP-1R in cancer and adjacent non-pathological breast tissues in BC patients with DM (125 cases) and without DM (58 cases). We then compared the status of GLP-1R with that of fibroblast growth factor 7 (FGF7) and fibroblast growth factor receptor 2 (FGFR2), Ki-67 labeling index (Ki-67 LI) and disease free survival (DFS) of the patients and also between cancerous and non-pathological breast tissues. Results: GLP-1R immunoreactivity was significantly higher (p = 0.044) in the patients with DM than without in carcinoma tissues. However, this was detected only in invasive carcinoma (p < 0.01) and not in non-invasive carcinoma nor non-pathological mammary glands. FGF7 was significantly correlated with the status of GLP-1R in BC (p = 0.045). In addition, in ER positive BC cases, those with GLP-1R positive status tended to have higher Ki-67 LI of more than 14% (p = 0.070). Conclusion: These findings all demonstrated the possible association between GLP-1R status and biological features of BC, especially of invasive BC in DM patients.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalBreast Cancer Research and Treatment
Volume189
Issue number1
DOIs
Publication statusPublished - 2021 Aug

Keywords

  • Breast cancer
  • Diabetes mellitus
  • Fibroblast growth factor 7
  • Fibroblast growth factor receptor 2
  • Glucagon-like peptide-1 receptor
  • Immunohistochemistry

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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