Response of myokines in breast cancer patients is dependent on the modality of acute exercise

Objectives. Physical activity influences anticancer effects (ACE) indirectly by reducing cancer risk factors like sex hormones, body fat, and inflammation (doi:10.1038/nrc2325). Preclinical studies show direct effects on cancer cells, such as reduced proliferation (doi:10.1016/j.cmet.2017.09.015). These effects may be mediated by myokines like IL-6, which can inhibit proliferation and induce apoptosis in breast cancer (BC) (doi:10.1515/tjb-2020-0508) and colon cancer cells (doi:10.1002/ijc.33982). Oncostatin M (OSM) and SPARC can suppress or promote cancer growth depending on the type of cancer. Exercise also stimulates release of BDNF, and FGF21, which have systemic or direct ACE effects (doi:10.1016/j.bbcan.2022.188761). This pilot study examined effect of acute exercise on serum myokine levels in BC survivors. The focus was on markers associated with cancer progression, immune response, and metabolism, including cytokines.
Materials and Methods. Seven women (age 44.7±7.76 years, BMI 24.4 (23.1; 30.3), 6-12 months post-BC treatment). Modified Bruce protocol was used to assess HRpeak and VO2peak (UNCCRI Treadmill Protocol). VO2peak attainment was determined based on modified Borg scale (fatigue rating ≥8), and/or RER ≥1.1, and tester’s confirmation of protocol termination. In the following weeks subjects completed three high-intensity exercise protocols (85–95% heart rate reserve) with different modalities: interval, continuous, and incremental. Blood samples were obtained before and immediately after each exercise session. Levels of IL-6, OSM, FGF-21, SPARC, and BDNF were analyzed using the Human Myokine Magnetic Bead Panel (HMYOMAG-56K, Millipore, Billerica, MA, USA) on a Magpix analyzer (Austin, TX, USA). After checking normality mixed-design ANOVA and Post-hoc comparisons were used for data analysis.
Results. During VO2peak estimation RER reached 1.14±0.0698, ventilation (VE) was 77±7.47 L/min and VO2peak 29.1±2.93 ml/kg/min. Data analysis revealed no significant interaction between intervention and time for any of the evaluated biomarkers (p>0.05). Furthermore, post-hoc comparisons showed no significant differences between interventions or time points for any biomarker (all p > 0.05). However, each patient showed a different intra-individual response to various high-intensity exercise modalities, with varying trends and magnitudes of change. For example, BDNF values before vs after the training session for one of the patients were as follows: interval training - 18,914.8 vs 6,689.3 pg/mL; continuous exercise - 13,551.4 vs 14,891.5 pg/mL; incremental exercise - 6,813.5 vs 11,788.1 pg/mL, correspondingly.
Conclusions. None of the high-intensity exercise modalities resulted in significant systemic changes of myokines in breast cancer patients. However, intra- and inter- individual variability in response to different exercise modalities should be considered for development of proper research design and for personalized interventions in this patient population.