Iron metabolism in breast cancer: mechanisms and therapeutic implications: a narrative review

Iron metabolism plays a crucial role in breast cancer progression by supporting rapid cell proliferation, metastasis, and therapy resistance. Breast cancer cells exhibit increased iron uptake through overexpression of transferrin receptor 1, leading to intracellular iron accumulation. Elevated ferritin levels further protect tumor cells from oxidative stress-induced damage, while reduced ferroportin expression limits iron export, creating an iron-rich microenvironment that favors tumorigenesis. These alterations in iron homeostasis contribute to an aggressive cancer phenotype and are associated with poor clinical outcomes. Beyond its role in tumor growth, dysregulated iron metabolism influences the tumor microenvironment by promoting angiogenesis and immune evasion. Iron-laden macrophages within the tumor stroma support cancer progression by supplying iron to malignant cells, fueling their metabolic demands. Moreover, iron-driven oxidative stress generates reactive oxygen species, leading to DNA damage, genomic instability, and the activation of pathways involved in epithelial-mesenchymal transition. These processes enhance breast cancer cell invasion and metastasis, particularly in aggressive subtypes such as triple-negative breast cancer.