Biomarker-driven neoadjuvant immunotherapy in triple-negative breast cancer: emerging therapeutic targets FOXP3 and WT1

Abstract

Despite advances in first-line therapy, a subset of breast cancer patients—particularly those with triple-negative breast cancer (TNBC)—continue to experience unfavorable prognosis. Recently, the addition of neoadjuvant immunotherapy has been intensively studied and widely adopted to improve clinical outcomes of patients with breast cancer. Based on encouraging results from large-scale clinical trials such as KEYNOTE-522 and IMpassion031, the range of drugs evaluated has expanded from atezolizumab to other programmed cell death protein 1/programmed cell death-ligand 1(PD-1/PD-L1) inhibitors, such as pembrolizumab and avelumab. Furthermore, the pursuit of targeted therapies has extended to other biomarkers, including Forkhead Box Protein P3 (FOXP3) and Wilms’ Tumor gene 1 (WT1). Despite these advancements, the heterogeneity in trial design, participant demographics, endpoints, and other confounding variables has resulted in divergent conclusions across clinical studies. In this review, we delineate the principal neoadjuvant immunotherapy biomarkers implicated in breast cancer and elucidate their action mechanisms. We also summarize the ongoing and reported clinical studies, aiming to offer a coherent perspective on the evolving role of neoadjuvant immunotherapy in breast cancer management.