Inflammatory and Nutritional Markers Predicting Pathological Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer: A Multicenter Real-World Study

<b>Background:</b> Pathological complete response (pCR) following neoadjuvant therapy (NAT) is a key surrogate marker for long-term outcomes in HER2-positive breast cancer. Identifying clinical and biological predictors of pCR, including systemic inflammatory and nutritional markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-albumin ratio (NAR), C-reactive protein-to-albumin ratio (CAR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI), may help refine treatment strategies and improve patient outcomes. <b>Methods:</b> We retrospectively analyzed 174 patients with stage II-III HER2-positive breast cancer who received neoadjuvant anti-HER2-based regimens at multiple centers between 2010 and 2025. Demographic, clinicopathological, and laboratory data were collected, and inflammatory and nutritional indices (NLR, PLR, LMR, NAR, CAR, SII, PNI) were calculated. Predictors of pCR were evaluated using univariate and multivariate logistic regression analyses. <b>Results:</b> Overall, 49% of patients achieved pCR. In multivariate analysis, independent predictors of pCR were hormone receptor negativity, smaller tumor size, HER2 IHC 3+ expression, dual HER2 blockade, and a higher prognostic nutritional index (PNI ≥ 55). In contrast, systemic inflammatory indices such as NLR, PLR, LMR, NAR, CAR, and SII were not significantly associated with pCR. <b>Conclusions:</b> This multicenter real-world study demonstrates that conventional inflammatory markers have limited predictive value, whereas the PNI emerges as a simple and practical biomarker reflecting nutritional and immune status. Integrating PNI with clinicopathological factors may enhance risk stratification and help guide individualized neoadjuvant treatment strategies in HER2-positive breast cancer.