Mitochondrial biology and immune crosstalk in breast cancer: therapeutic opportunities and challenges

Mitochondria are central regulators of breast cancer progression and therapy response, acting beyond energy metabolism to integrate redox balance, regulated cell death, metabolic plasticity, and immune signaling. This review summarizes how mitochondrial metabolism, dynamics, stress signaling, and quality-control pathways shape tumor heterogeneity, immune evasion, and treatment outcomes across tumor, immune, and stromal compartments. In breast cancer, subtype-specific mitochondrial programs influence oxidative phosphorylation, fatty acid oxidation, glutaminolysis, lactate accumulation, and mtDAMP signaling, thereby contributing to immune suppression and therapeutic resistance. We further discuss how mitochondrial regulation of apoptosis, ferroptosis, cuproptosis, and pyroptosis reveals both therapeutic opportunities and unresolved limitations. Although mitochondria-targeted strategies show translational promise, their clinical application remains constrained by metabolic heterogeneity, adaptive rewiring, immune-cell liability, and insufficient biomarkers. Overall, mitochondria represent a context-dependent therapeutic axis in breast cancer.