Aerobic Exercise and Mediterranean Diet Modulate IGF-1 and Binding Proteins in Breast Cancer Survivors

For breast cancer survivors (BCS), obesity-related biomarkers like insulin-like growth factor-1 (IGF-1) are crucial for identifying individuals at high risk who could benefit from lifestyle interventions (LIs). Dysregulation of IGF-1 is linked to increased cancer risk and progression. While professional organizations recommend weight management, the precise effect of LIs on modulating IGF-1 levels in BCS has remained inconclusive, highlighting a gap in personalized intervention strategies.

Fifty inactive breast cancer survivors were randomized into a control group (CG, n=26) and an intervention group (IG, n=24). Both groups received general recommendations on exercise and the Mediterranean diet. The IG additionally followed a supervised 3-month aerobic exercise program (MoviS trial, NCT04818359). Researchers assessed associations between baseline and LI-induced changes (∆) in IGF-1, IGF binding protein-1 (IGFBP1), and IGFBP3 levels, alongside anthropometric, metabolic, and fitness parameters using linear and quadratic models.

Both groups significantly increased physical activity (measured in MET min/week) and Mediterranean diet adherence (via MeDiet score) after the lifestyle intervention. Maximal oxygen uptake (V̇O2max) increased exclusively in the IG. Significant reductions were observed in BMI, fat mass, insulin levels, HOMA-IR index, total cholesterol, and LDL cholesterol in both groups. These metabolic improvements were strongly associated with increased IGFBP1 and decreased IGFBP3 levels. Mean IGF-1 levels remained unchanged across the groups; however, a crucial baseline-dependent modulation was identified: > Participants with baseline IGF-1 ≤ 94.7 ng/mL showed increases post-intervention, whereas those with IGF-1 ≥ 173.3 ng/mL exhibited decreases. Similar trends were found for IGFBP3 but not for IGFBP1. A three-dimensional quadratic model revealed a U-shaped relationship between baseline IGF-1, ∆ IGF-1, and ∆ V̇O2max, indicating that V̇O2max improvements correlated with IGF-1 increases in low-baseline participants and decreases in high-baseline participants.