Neoadjuvant Immunotherapy in Triple-Negative Breast Cancer: Striking Potential or Need for Caution?

Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited targeted therapies and a substantial unmet clinical need. Immunotherapy has emerged as a transformative frontier in TNBC, with immune checkpoint inhibitors (ICIs) representing a major category of this approach. The KEYNOTE-522 trial established pembrolizumab, an ICI, combined with chemotherapy as a standard neoadjuvant regimen for TNBC. However, the clinical outcomes of neoadjuvant immunotherapy-containing regimens are influenced by multiple factors, including the specific immunotherapeutic agents employed, companion strategies (such as distinct chemotherapy backbones or antibody-drug conjugates), patient characteristics, and trial design. Therefore, the implementation of neoadjuvant immunotherapy in broader clinical practice should be approached with caution. Elderly patients (≥65 years, over one-quarter of all breast cancer cases) may experience reduced efficacy from immunotherapy due to immunosenescence and are more susceptible to treatment-associated toxicity. Leveraging the neoadjuvant setting for biomarker-driven risk stratification will be essential to guide age-tailored treatment optimization and minimize unnecessary toxicity. This perspective highlights the opportunities and challenges associated with neoadjuvant immunotherapy in TNBC and outlines future directions for optimizing its clinical application.