Targeting metabolic dysregulation in postmenopausal breast cancer: Synergistic effects of nutrition-based interventions and exercise on molecular and cellular pathways

Cancer Cell Int. 2026 May 21. doi: 10.1186/s12935-026-04321-3. Online ahead of print.

ABSTRACT

Postmenopausal females diagnosed with breast cancer who are undergoing aromatase inhibitor (AI) therapy often exhibit metabolic disturbances, which may manifest as insulin resistance, dyslipidemia, increased adiposity, and an elevated risk of cardiovascular events. Such metabolic disruptions have the potential to undermine the efficacy of treatment and intensify therapy-related adverse effects, thereby diminishing overall quality of life. The implementation of functional nutrition and exercise-based interventions has emerged as a viable adjunctive therapeutic strategy aimed at addressing these metabolic complications by influencing fundamental mechanistic pathways, including chronic inflammation, oxidative stress, hormonal imbalances, and mitochondrial dysfunction. This review systematically investigates the phenomenon of metabolic dysregulation within this specific patient demographic and emphasizes the impact of particular dietary constituents in conjunction with organized aerobic and resistance training on critical metabolic regulators, including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors, and insulin signaling cascades. The therapeutic efficacy associated with the incorporation of these lifestyle modifications is examined within the framework of optimizing glucose homeostasis, lipid profiles, and attenuating systemic inflammation. Comprehending these mechanistic pathways establishes a basis for the formulation of personalized functional nutrition and exercise protocols designed to alleviate metabolic adverse effects induced by artificial intelligence, augment therapeutic outcomes, and enhance overall health in individuals diagnosed with postmenopausal breast cancer.

PMID:42169109 | DOI:10.1186/s12935-026-04321-3