Post-Radiotherapy Changes in Circulating Dodecanoic Acid Identify Metabolic Phenotypes Associated with Recurrence in Breast Cancer

Research on biomarkers reflecting tumor biology and systemic metabolism is crucial for improving the accuracy and personalization of breast cancer (BC) prognosis. We investigated circulating dodecanoic acid in 229 patients undergoing radiotherapy (RT) and assessed its association with progression-free survival and overall survival over six years. Patients were classified into two phenotypes based on post-RT changes in dodecanoic acid: The Increase Phenotype (IP) had lower baseline concentrations and showed a post-RT rise, whereas the Decrease Phenotype (DP) had higher pre-RT levels and declined after treatment. Dodecanoic acid levels were lower in tumors than in peritumoral samples, and their association with phenotypes varied by sampling region, suggesting that systemic changes reflect broader metabolic adaptations rather than local tissue concentrations. Post-RT increases in dodecanoic acid were associated with higher paraoxonase-1 activity, suggesting a link with antioxidant status. Patients in the IP group had a significantly lower risk of progression than those in the DP group, whereas no significant differences in overall survival were observed. These findings highlight the potential utility of dodecanoic acid measurement as a prognostic biomarker and suggest that modulating fatty acid metabolism could be explored as a therapeutic strategy.