Introduction: Diabetes mellitus (DM) has been generally considered one of the risk factors of breast cancer (BC) development. Glucagon-like-peptide-1 (GLP-1) has been reported to be associated with increased risks of cancer development in some human malignancies. Koehler,reported that GLP-1 analogues could be associated with intestinal tumor growth through increased Fibroblast Growth Factor 7 (FGF7). However, the involvement of GLP-1 has not been studied in BC. Therefore, in this study, we explored the possible association of GLP-1 with BC risk in DM patients, by comparing GLP-1 receptor (GLP-1R), FGF7 and Fibroblast Growth Factor Receptor2 (FGFR2) status of BC between DM and non-DM BC patients.

Method: We immunolocalized GLP-1R, FGFR2 and FGF7, the ligand of FGFR2 in 125 BC cases with DM and 57 without DM (NDM), operated from 2005 to 2013 and 2017 at Nahanishi Clinic and Tohoku University Hospital, Japan, excluding those who received neoadjuvant chemotherapy.

Result: The status of GLP-1R was significantly more frequent in BC tissue (Ca) than in normal mammary gland tissue (NCa) regardless of DM (DM Ca 67.2% vs NCa 19.5% P<0.001, NDM Ca 51.7% vs NCa 16.4% P<0.001). That of GLP-1R in Ca of the DM group was significantly more frequent than in the NDM group (DM 67.2% vs NDM 51.7% P=0.044). That of FGFR2 was significantly more frequent in Ca than NCa of DM group (Ca 92% vs NCa 59.3% P<0.01), although no significant difference detected in NDM group (Ca 82.8% vs NCa 74.5% P=0.29). There were no significant differences of FGFR2 status in BC between the DM and NDM groups (DM 92% vs NDM 82.8% P=0.062). H score of FGF7 tended to be higher in Ca than NCa in the DM group (Ca 176.5 vs NCa 158.5 P=0.058) but this was not detected in the NDM group (Ca 166.3 vs NCa 161.1 P=0.7). The status of FGF7 in Ca was not different between the DM and NDM groups (DM 176.5 vs NDM 166.3 P=0.37). That of FGF7 in Ca harboring GLP-1R was significantly higher than Ca without GLP-1R regardless of DM (DM GLP-1R+ 189.4 vs GLP-1R- 150 P<0.01, NDM GLP-1R+ 185.5 vs GLP-1R- 146.4 P<0.01) with the same findings obtained in NCa tissue (DM GLP-1R+ 237.8 vs GLP-1R- 137.8 P<0.001, NDM GLP-1R+ 228.8 vs GLP-1R- 149.3 P=0.032).

Conclusion: Results of our present study did demonstrate that GLP-1R was more frequently detected in BC tissue than in normal mammary gland tissue with more pronounced in DM patients. These results also indicated an association between GLP1 and FGF7 in the development of BC in DM patients.

Citation Format: Naoko Takigami, Shimpei Kuniyoshi, Yasuhiko Miki, Kentaro Tamaki, Yoshihiko Kamada, Kano Uehara, Seiko Tsuchiya, Shigeharu Terukina, Takanori Ishida, Minoru Miyashita, Ayako Kanai, Keely May McNamara, Nobumitsu Tamaki, Hironobu Sasano. The possible association among breast cancer, diabetes mellitus and GLP-1 receptor [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-02-10.