The Role of Irisin and Physical Activity in Breast Cancer

Irisin, a myokine released during physical activity, has been proposed as a mediator of exercise's protective effects against breast cancer (BC). This review underscores the critical role of irisin in mediating the anticancer effects of exercise and its potential application in BC prevention and prognosis.

Studies published up to 2025 were identified in PubMed, Scopus, and Web of Science databases. Data from experimental models, clinical trials, and observational studies were analyzed with emphasis on exercise-induced irisin secretion and its effects on cancer-related pathways.

Irisin, derived from the precursor FNDC5 upon PGC-1α activation in skeletal muscle, regulates cancer-associated pathways by activating AMP-activated protein kinase (AMPK), inhibiting mammalian target-of-rapamycin (mTOR), modulating phosphoinositide 3-kinase (PI3K)/Akt and nuclear factor kappa B (NF-κB) signaling, and influencing transforming growth factor beta (TGF-β) activity. These actions reduce chronic inflammation, tumor proliferation, angiogenesis, and epithelial-mesenchymal transition, while enhancing apoptosis and metabolic balance. Preclinical studies demonstrate irisin's capacity to limit BC cell viability, migration, and metastasis. Clinically, higher circulating irisin levels correlate with reduced tumor aggressiveness, fewer metastases, and better survival, though tumor may overexpress irisin as a local adaptive response. Regular moderate physical activity appears most effective in stimulating irisin secretion, although optimal exercise parameters remain to be determined.

Irisin exerts multifaceted anticancer effects and holds promise as a biomarker and therapeutic target in BC. Its role as a mediator of exercise benefits supports the inclusion of regular moderate physical activity in BC prevention and prognosis strategies. Further research is needed to define clinical applications and optimal exercise regimens for maximizing irisin potential.