Abstract P6-11-09: Effects of a 12 Week Breast Cancer Exercise Program on the Mitochondrial Derived Peptide MOTS-c
Authors: Shen Chloe , Baron Kirsten , Toyama Matthew , Cohen Pinchas , Wan Junxiang , Kumagai Hiroshi , Pagano Ian , Yamada Paulette , Teranishi-Hashimoto Cheri , Fukui Jami 
Published: March 2023

Abstract
Background: Breast cancer survivors have an increased risk for comorbid conditions such as cardiovascular disease, diabetes, and hypertension. In addition, cancer related treatments negatively affect bone health, muscular strength, and quality of life. Exercise is an effective strategy to combat cancer related symptoms (fatigue, anxiety) and common comorbid conditions. MOTS-c is a Mitochondrial Derived Peptide (MDP) that has a number of beneficial effects on metabolism, insulin sensitivity, and exercise capacity. Previously published preclinical studies have shown that MOTS-c treatment improves physical performance in young, middle-age, and old mice. In humans, it has been implicated to promote metabolic homeostasis, stimulate glucose utilization, fat-oxidation, reduce inflammation, and protect against both cardiovascular and metabolic disease. We implemented a 12-week exercise program in breast cancer survivors. We evaluated changes in baseline and post12-week MOTS-c levels and corresponding body composition changes.
Methods: We evaluated 25 participant paired samples at baseline and post 12-weeks of exercise. Participants engaged in a 12-week exercise program, 3 times a week for 90 minutes/session. At baseline and post 12-weeks, participants underwent a DXA scan, body composition analysis, and a blood draw. The blood samples were analyzed using an in-house ELISA and compared to various clinical and body composition metrics.
Results: The median age was lowest for the high responders (56.7 years) compared to moderate responders (57 years) and reduced MOTS-c (61.5 years). We found 3 distinct groups: reduced MOTS-c with exercise (n=8), increased MOTS-c moderate responders (0-10pg/ml; n=2), and increased MOTS-c high responders (&gt;10 pg/ml; n=15). MOTS-c had an inverse relationship with almost all tested metrics including: age, weight, BMI, waist to hip ratio, body composition—visceral (fat area, fat mass, fat volume), subcutaneous fat mass, whole body (body lean, body mass, body percent fat, bone mineral content (BMC), and bone mineral density (BMD). Although the majority of the metrics improved and had inverse relationships for MOTS-c, the reduced MOTS-c group had increased BMC and BMD. Interestingly, despite a higher MOTS-c value, there was an increase in visceral fat as well as an increase in whole body fat across all groups. Of the 25 participants, 22 were Asian, two were Caucasian, and one was Native Hawaiian/Pacific Islander. Given the small number of participants, there does not appear to be any correlation between MOTS-c and ethnicity in our study.
Summary: We found significant changes in MOTS-c according to clinical and body composition metrics after a 12-week exercise program. The findings in this study support previous findings on MOTS-c metrics including MOTS-c levels decreasing with age. However, there are few clinical trials evaluating MOTS-c in cancer survivors. MOTS-c is a potential biomarker related to exercise in cancer survivors. Our study was predominantly conducted in Asian women where there is limited data. This emphasizes the need for more clinical trials to be conducted with racially/ethnically diverse populations to better understand MOTS-c’s role in our varied cancer populations.

Citation Format: Chloe Shen, Kirsten Baron, Matthew Toyama, Pinchas Cohen, Junxiang Wan, Hiroshi Kumagai, Ian Pagano, Paulette Yamada, Cheri Teranishi-Hashimoto, Jami Fukui. Effects of a 12 Week Breast Cancer Exercise Program on the Mitochondrial Derived Peptide MOTS-c [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-11-09.