Correlation Between Interleukin-33 Expression and Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Abstract

Introduction: Locally advanced breast cancer (LABC) is associated with high morbidity. While neoadjuvant chemotherapy (NAC) is the standard of care, clinical responses vary significantly due to tumor heterogeneity. This study evaluated pre-treatment intracellular Interleukin-33 (IL-33) expression as an independent predictor of NAC response in LABC patients. Methods: This prospective cohort study included 54 female LABC patients at Hasanuddin University Hospital. Pre-treatment IL-33 protein expression was evaluated semiquantitatively using immunohistochemistry. All subjects received three cycles of taxane- and anthracycline-based NAC. Post-chemotherapy clinical responses were assessed using RECIST guidelines. Data were analyzed via bivariate and multiple logistic regression models. Results: Most subjects presented with histologic grade 3 tumors (64.8%) and the luminal molecular subtype (57.4%). Positive intracellular IL-33 expression was detected in 40 patients (74.1%), with 33 patients (61.1%) achieving a favorable clinical response to NAC. The IL-33 positive cohort demonstrated a significantly higher response rate compared to the negative cohort (70.0% vs. 35.7%; p = 0.024; OR = 4.2; 95% CI: 1.16–15.19). Multivariate modeling confirmed that positive IL-33 expression (Adjusted OR = 5.01; 95% CI: 1.12–22.32; p 0.035) and the luminal subtype (Adjusted OR = 8.73; 95% CI: 2.29–33.28; p = 0.002) are robust independent predictors of clinical outcomes. Conclusion: Pre-treatment intracellular IL-33 expression is a significant independent predictor of NAC response in LABC. This biomarker demonstrates substantial potential in assisting patient stratification to optimize precision oncology.