Unlocking ferroptosis: A novel link between triple-negative breast cancer and immune regulation

Abstract

Breast cancer is the most diagnosed malignant tumor worldwide and remains the leading cause of cancer-related death among women. Among its subtypes, triple-negative breast cancer (TNBC) is the most aggressive form, resulting in limited treatment options and a poorer prognosis. The development of novel therapeutic strategies is both urgent and challenging. Ferroptosis is a recently identified form of regulated cell death that is iron-dependent and characterized by the abnormal accumulation of lipid peroxides and iron ions. Ferroptosis is critical for tumorigenesis, progression, metastasis, and therapeutic resistance in breast cancer, positioning its modulation as a promising complementary strategy. Furthermore, the tumor microenvironment is affected by either inhibiting or inducing ferroptosis in immune cells—promoting tumor proliferation, therapeutic resistance, or, in combination with radiotherapy, antioxidants, or ferritinophagy activators, facilitating tumor eradication. Despite the expanding literature on ferroptosis and cancer, a critical gap remains in understanding how ferroptosis operate in tumor cells versus immune cells within the TNBC microenvironment. This lack of integration hampers the rational design of therapeutic strategies that induce ferroptosis in cancer cells while preserving- or enhancing-antitumor immunity. This review addresses this gap by providing a unified framework linking ferroptosis, immune regulation, and emerging therapeutic strategies in TNBC.