Ferroptosis in Breast Cancer: Linking Iron Metabolism, Intertumoral Heterogeneity, and Predictive Biomarkers of Clinical Response

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ID: 332867
2026
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Abstract
Abstract Breast cancer (BC) is a prevalent and heterogeneous neoplasm whose therapeutic resistance remains a major challenge. Ferroptosis, an iron-dependent form of regulated cell death that is characterized by lipid peroxidation, has emerged as a key mechanism linking iron metabolism, oxidative stress, and tumor aggressiveness. The objective for this narrative review was to summarize the principal mechanisms regulating ferroptosis in BC and discuss its potential as a therapeutic target. A literature review was conducted to investigate the mechanisms involved in ferroptosis in BC, with emphasis on iron metabolism, oxidative stress, lipid peroxidation, antioxidant defense systems, and differences in ferroptosis sensitivity among BC subtypes. The literature indicates intracellular iron accumulation increases reactive oxygen species generation and enhances the susceptibility of cancer cells to ferroptosis. This process is mainly controlled by the glutathione peroxidase 4–glutathione and ferroptosis suppressor protein 1–coenzyme Q10 antioxidant systems, which neutralize lipid peroxides and preserve membrane integrity. Dysregulation of these pathways contributes to redox imbalance and disease progression. Among BC subtypes, triple-negative tumors show greater sensitivity to ferroptosis due to heightened oxidative activity and reduced expression of protective enzymes, whereas luminal and Human epidermal growth factor receptor 2–positive tumors exhibit increased resistance. Controlled induction of ferroptosis may help eliminate drug-resistant cells and enhance treatment efficacy, reinforcing its relevance as a central axis connecting metabolism, oxidative stress, and programmed cell death.
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Authors Jheniffer da S Sousa, Rodrigo S P Lima, Maria Shelda de O Neres, Irislene Costa Pereira, Jorddam Almondes Martins, Dallyla J M de Sousa, Rebeca Lima Monteiro, Juliana S Severo, Francisco Leonardo Torres‐Leal
Journal nutrition reviews
Year 2026
DOI
10.1093/nutrit/nuag149
URL
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