Dose-dependent effects of aerobic exercise on clinically relevant biomarkers among healthy women at high genetic risk for breast cancer: A secondary analysis of a randomized controlled study

Background: Excess adiposity and dysregulated metabolism are associated with increased cancer risk. Triglycerides, cholesterol, glucose, insulin, HOMA-IR, and VO₂max are robust clinical-metabolic biomarkers of overall health. Aims: Aerobic exercise may improve clinical-metabolic biomarkers and decrease cancer risk. This secondary analysis of the WISER Sister randomized controlled trial investigated dose-dependent effects of aerobic exercise on clinical biomarker levels in women at high genetic risk for breast cancer. Methods and Results: One hundred thirty-nine participants were randomized to: control (<75 min/week), low-dose (150 min/week), and high-dose (300 min/week) aerobic exercise intervention groups. Intervention adherence was assessed via heart monitor. Fasting blood draws, cardio-pulmonary tests, and demographical surveys were taken at baseline and 5 months. Triglyceride, cholesterol, glucose, insulin, and VO₂max changes were assessed for 80 of the 122 study completers. Ninety-six percent of assayed-completers adhered to >80% of their exercise dose. A significant dose-dependent increase in VO₂max was observed for the low-dose and high-dose groups compared to control. No intervention effects were observed for plasma biomarkers. Overweight women (BMI > 25) showed a significant decrease in insulin levels and a trend for decreased triglycerides following exercise intervention. Significant increases in VO₂max were independent of BMI stratification. Conclusion: Women at high genetic risk for breast cancer should maintain healthy weights and aerobic capacities through aerobic exercise to achieve measurable benefits on overall health. For overweight women, exercise appears to improve subclinical metabolic dysregulation. However, normal weight women were unaffected by aerobic exercise as their biomarker levels may be below the threshold for improvement. VO₂max increases solely quantified the benefits of exercise in already healthy women at high-risk for breast cancer.