The Role of Redox-Regulating Enzymes in Inoperable Breast Cancers Treated with Neoadjuvant Chemotherapy

Although validated predictive factors for breast cancer chemoresistance are scarce, there is emerging evidence that the induction of certain redox-regulating enzymes may contribute to a poor chemotherapy effect. We investigated the possible association between chemoresistance and cellular redox state regulation in patients undergoing neoadjuvant chemotherapy (NACT) for breast cancer. In total, 53 women with primarily inoperable or inflammatory breast cancer who were treated with NACT were included in the study. Pre-NACT core needle biopsies and postoperative tumor samples were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), thioredoxin (Trx), and peroxiredoxin I (Prx I). The expression of all studied markers increased during NACT. Higher pre-NACT nuclear Prx I expression predicted smaller size of a resected tumor (p = 0.00052; r = -0.550), and higher pre-NACT cytoplasmic Prx I expression predicted a lower amount of evacuated nodal metastasis (p = 0.0024; r = -0.472). Pre-NACT nuclear Trx expression and pre-NACT nuclear Keap1 expression had only a minor prognostic significance as separate factors, but when they were combined, low expression for both antibodies before NACT predicted dismal disease-free survival (log-rank p = 0.0030). Our results suggest that redox-regulating enzymes may serve as potential prognostic factors in primarily inoperable breast cancer patients.