Association of Pretreatment Serum Albumin and Systemic Inflammatory Markers with Pathologic Response to Neoadjuvant...

Background: Pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer is influenced by multiple tumor- and host-related factors, and readily available pretreatment biomarkers of response are still limited. This study aimed to evaluate the association between pretreatment systemic inflammatory and nutritional parameters and pCR assessed by the Miller-Payne grading system, with a specific focus on the independent predictive value of pretreatment serum albumin compared with established inflammatory ratios. Methods: A total of 226 patients with breast carcinoma who received NACT between May 2017 and September 2023 were retrospectively evaluated. Pretreatment laboratory parameters-including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), serum albumin, and the CRP/albumin ratio (CAR)-were recorded. Pathological response was assessed using the Miller-Payne grading system by two breast pathologists blinded to laboratory data. Univariable and multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed, complemented by bootstrap validation of the optimal cut-off, a sensitivity analysis using the contemporary ypT0/is ypN0 definition of pCR, and a subgroup analysis by molecular subtype. Results: pCR was observed in 41 patients (18.1%). Pretreatment serum albumin levels were significantly lower in responders than in non-responders (p = 0.027), whereas NLR, PLR, CRP, and CAR were not significantly associated with response. In multivariable analysis, pretreatment serum albumin, Ki-67, and HER2 status emerged as independent predictors of pCR. ROC analysis demonstrated moderate discriminatory ability for albumin (AUC = 0.64); the optimal cut-off was 4.22 g/dL (bootstrap 95% CI 3.50-4.53 g/dL), with values below this threshold associated with a higher likelihood of pCR. The association between low pretreatment albumin and pCR was particularly pronounced in the triple-negative subgroup (3.30 vs. 4.02 g/dL, p = 0.027). The albumin signal remained significant under the stricter ypT0/is ypN0 definition of pCR in univariable analysis (OR 0.47, p = 0.045). Conclusions: Pretreatment serum albumin, independent of systemic inflammatory ratios, is associated with pCR to NACT in breast cancer and may serve as a candidate biomarker for pretreatment risk stratification, particularly when interpreted alongside established tumor-related predictors such as Ki-67 and HER2 status. The association appears especially relevant in the triple-negative subgroup, suggesting that patients with TNBC and low pretreatment serum albumin may warrant heightened multidisciplinary attention during NACT. Validation in larger, prospective, multicenter cohorts is needed before routine clinical implementation.