Exploratory evaluation of CA 15-3 × NLR score for predicting pathologic complete response in breast cancer patients undergoing neoadjuvant chemotherapy

Abstract

Purpose: This study aimed to evaluate the predictive role of the CA 15-3 × neutrophil-to-lymphocyte ratio (NLR) score in estimating pathologic complete response (pCR) in patients with invasive breast cancer who underwent neoadjuvant chemotherapy (NACT).

Methods: A total of 330 patients treated with NACT between January 2015 and March 2025 were retrospectively analyzed. The CA 15-3 × neutrophil-to-lymphocyte ratio (NLR) score was calculated by multiplying pre-treatment serum CA 15-3 levels with the NLR. pCR was defined as the absence of invasive carcinoma in both the breast and axillary lymph nodes after surgery. Logistic regression analyses were performed to identify independent predictors of pCR, and receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cutoff value for the composite score.

Results: The median age of the study population was 48 years. Pathologic complete response was achieved in 42.4% of patients. The median CA 15-3 × NLR score was significantly lower in the pCR group compared to the non-pCR group (21 vs. 24; p = 0.033). ROC analysis revealed an optimal cutoff value of ≤ 32.7 (AUC = 0.568), with 81.05% sensitivity and 33.9% specificity. In multivariate logistic regression analysis, CA 15-3 × NLR ≤ 32.7 remained an independent predictor of pCR (OR 1.931; 95% CI 1.086-3.433; p = 0.025), along with N stage 2 and the absence of perineural invasion.

Conclusion: The CA 15-3 × NLR score demonstrates modest prognostic potential in predicting treatment response in breast cancer patients receiving neoadjuvant chemotherapy. While promising, these findings should be interpreted cautiously, and further validation is needed before clinical implementation.

Keywords: Breast cancer; CA 15-3; NLR; pCR.