Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial

Authors

Justin C. Brown, LSU Health Sciences Center - New OrleansFollow
Guillaume Spielmann, Louisiana State University, Baton Rouge, LA
Shengping Yang, Pennington Biomedical Research Center, Baton Rouge, LA
Stephanie L.E. Compton, Pennington Biomedical Research Center, Baton Rouge, LA
Lee W. Jones, Memorial Sloan-Kettering Cancer Center, New York, NY
Melinda L. Irwin, Yale University, New Haven, CT
Jennifer A. Ligibel, Dana-Farber Cancer Institute, Boston, MA
Jeffrey A. Meyerhardt, Dana-Farber Cancer Institute, Boston, MA

Document Type

Article

Publication Date

6-18-2024

Publication Title

Journal of Cachexia, Sarcopenia and Muscle

Abstract

Background: Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. Methods: This hypothesis-generating analysis used biospecimens collected from a multi-centre 2 × 2 factorial randomized design of 116 patients with stage I–III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log-transformed, and main effects analyses were conducted using linear mixed-effects regression models. The type I error rate was controlled with the Holm sequential testing procedure. Results: Randomization to exercise increased leukaemia inhibitory factor (1.26 pg/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted P = 0.001) and interleukin-15 (2.23 pg/mL, 95% CI: 0.87, 3.60; adjusted P = 0.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (−2.69 pg/mL, 95% CI: −4.31, −1.07; adjusted P = 0.014) and interleukin-15 (−1.74 pg/mL, 95% CI: −2.79, −0.69; adjusted P = 0.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons. Conclusions: This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis-generating observation warrants further basic, translational and clinical investigation and replication.

PubMed ID

38887915

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Brown, Justin C.; Spielmann, Guillaume; Yang, Shengping; Compton, Stephanie L.E.; Jones, Lee W.; Irwin, Melinda L.; Ligibel, Jennifer A.; and Meyerhardt, Jeffrey A., "Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial" (2024). School of Medicine Faculty Publications. 2710.
https://digitalscholar.lsuhsc.edu/som_facpubs/2710
10.1002/jcsm.13509