Abstract
BACKGROUND: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is a surrogate for long-term outcomes in breast cancer, yet response rates vary widely. Biomarkers are needed to predict efficacy. Vitamin D, through its receptor-mediated diverse biological effects on tumor biology and immune regulation, has been suggested as a potential predictor of pCR.
METHODS: We retrospectively evaluated breast cancer patients who received NACT between December 2022 and December 2024. Baseline serum vitamin D and inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), and atherogenic index of plasma (AIP), were assessed. Pathological response was defined as pCR or Miller-Payne grades 4-5. ROC analysis identified optimal cut-offs, and logistic regression was applied to explore factors associated with pathological response.
RESULTS: Among 223 patients, pCR occurred in 39.0%. ROC analysis identified 14.5 ng/mL as the optimal vitamin D threshold (AUC 0.705, p < 0.001). Vitamin D ≥ 14.5 ng/mL was independently associated with higher response, particularly in HR + /HER2 - and HER2 + subtypes; multivariable analyses also supported significance in TNBC. Recent vitamin D supplementation before NACT was significantly correlated with improved outcomes. Elevated CAR and AIP were inversely associated with response.
CONCLUSIONS: Vitamin D levels above 14.5 ng/mL independently predicted superior pathological response to NACT, with subtype-specific effects. Both baseline status and supplementation may enhance chemosensitivity, supporting vitamin D as a clinically relevant predictive biomarker.