Low Skeletal Muscle Index as a Predictor of Pathological Complete Response in HER-2 Positive and Triple-Negative...

Background and Objectives: Breast cancer is a leading cause of cancer-related mortality, particularly in aggressive subtypes such as HER2-positive and triple-negative breast cancer (TNBC). Achieving a pathological complete response (pCR) after neoadjuvant therapy is strongly associated with improved survival outcomes in these subgroups, making the prediction of pCR a clinical priority. Sarcopenia, a progressive loss of skeletal muscle mass and strength, is increasingly recognized in cancer patients and has been linked to chemotherapy toxicity and poorer survival. However, its specific impact on pCR in HER2-positive and TNBC patients remains unclear. This study aimed to evaluate the association between radiologically defined sarcopenia, or a low skeletal muscle index (SMI), and pathological response in these subtypes, and to explore its potential as a predictive biomarker. Materials and Methods: This retrospective study included patients with HER2-positive or TNBC who received neoadjuvant therapy between January 2015 and October 2023. SMI was assessed using pre-treatment positron emission tomography images at the L3 vertebral level, with values < 38.5 cm²/m² considered as low. Univariate and multivariate logistic regression analyses were performed to identify factors associated with pCR. Results: A total of 85 patients were included, with low SMI present in 35 (41.2%). In univariate analysis, clinical stage and low SMI were associated with pCR. However, in the multivariate model, only low SMI remained an independent predictor. Patients without low SMI had higher odds of achieving pCR (odds ratio [OR] 4.13; 95% confidence interval [CI] 1.55-10.95; p = 0.004). Low SMI was also associated with higher rates of treatment-related toxicity (42.9% vs. 20.0%, p = 0.023). Conclusions: Pre-treatment low SMI is strongly associated with lower pCR rates in patients with HER2-positive and TNBC undergoing neoadjuvant therapy. These findings underscore the importance of early identification and management of radiologically defined sarcopenia to optimize treatment response and improve clinical outcomes.