Lifestyle intervention based on aerobic exercise and Mediterranean diet modulates IGF-1 and its binding proteins in breast cancer survivors

Obesity-related biomarkers such as insulin-like growth factor-1 (IGF-1) may help identify high-risk breast cancer survivors (BCS) who could benefit from lifestyle interventions (LIs). However, the effect of LIs on modulation of IGF-1 levels in BCS remains inconclusive. Fifty inactive BCS were randomized into a control group (CG, n = 26) and an intervention group (IG, n = 24). Both groups received recommendations on exercise and the Mediterranean diet; the IG additionally followed a supervised 3-month aerobic exercise program (MoviS trial, NCT04818359). Associations between baseline and LI-induced changes (∆) in IGF-1, IGF binding protein-1 (IGFBP1) and IGFBP3 levels, along with anthropometric, metabolic, and fitness parameters, were assessed using linear and quadratic models. Both groups increased physical activity (MET min/week) and Mediterranean diet adherence (MeDiet score) after the LI, while maximal oxygen uptake (V̇O2max) increased only in the IG. Reductions in BMI, fat mass, insulin levels, HOMA-IR index, total and LDL cholesterol were observed in both groups and were associated with increased IGFBP1 and decreased IGFBP3 levels. Mean IGF-1 levels remained unchanged in both groups. Baseline IGFBP1 was inversely correlated with IGF-1, LDL, BMI, fat mass, and insulin, while baseline IGFBP3 was positively correlated with IGF-1, insulin, and HOMA-IR. Baseline IGF-1 levels were negatively correlated with ∆ IGF-1: participants with IGF-1 ≤ 94.7 ng/mL showed increases, whereas those with IGF-1 ≥ 173.3 ng/mL exhibited decreases post-intervention. 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: improvements in V̇O2max were associated with IGF-1 increase in participants with low baseline IGF-1 and decrease in those with high levels. Conversely, an inverted U-shaped relationship was found between baseline IGF-1, ∆ IGF-1, and ∆ fat mass. These findings underscore the importance of accounting for IGFBP modulation and baseline heterogeneity in IGF-1 levels when evaluating the efficacy of LIs targeting the IGF-1 system in high-risk BCS. Trial registration ClinicalTrials.gov NCT04818359. Registration Date 26 March 2021.