Sarcopenia in breast cancer: prognostic values and emerging therapeutic strategies

Breast cancer remains the most commonly diagnosed malignancy in women, yet treatment tolerance and long-term outcomes remain heterogeneous. Sarcopenia, a syndrome of progressive skeletal muscle loss, has emerged as a critical host factor in breast cancer, with prevalence ranging from 12% to 49% across the perioperative and neoadjuvant settings. Low muscle mass robustly predicts inferior overall and disease-free survival, reduced pathological complete response rates, heightened chemotherapy toxicity, and increased postoperative morbidity, particularly following complex autologous reconstruction. Integrating muscle metrics with systemic inflammatory indices further refines prognostic discrimination, while myosteatosis identifies patients with preserved muscle bulk but compromised metabolic fitness. Importantly, sarcopenia is potentially modifiable. Multimodal interventions centered on resistance training, protein optimization, and oral nutritional support show preliminary efficacy in preserving lean mass and attenuating treatment-related adverse effects. Emerging pharmacological strategies targeting the GDF-15-GFRAL and myostatin axes, alongside repurposed agents such as pindolol and sulfasalazine, offer promise for refractory cancer cachexia. Nevertheless, diagnostic heterogeneity and a paucity of breast cancer-specific randomized evidence continue to impede clinical translation. Standardized perioperative assessment, prospective prehabilitation trials, and scalable screening cascades are urgently needed to elevate muscle health from a passive biomarker to an active therapeutic target.