Recent advancements have illuminated the pivotal role of lipid metabolism in breast cancer, particularly the aggressive triple-negative subtype. This analysis delves into how disruptions in lipid regulation profoundly affect cancer cell behavior, influencing growth, metastasis, and treatment response. By examining key metabolic pathways and their interactions with cellular processes, researchers are uncovering new therapeutic targets to combat this complex disease.

Alterations in fatty acid, cholesterol, sphingolipid, and glycolipid metabolism significantly impact breast cancer cells' survival and invasiveness. Tumor cells exhibit an increased uptake and biosynthesis of fatty acids, which not only meet energy demands but also support membrane synthesis and signaling mechanisms. Enzymes such as CD36, FASN, and FABP4 play crucial roles in facilitating these metabolic changes, promoting tumor proliferation and metastatic potential. In cholesterol metabolism, elevated synthesis and metabolites like 27-hydroxycholesterol accelerate tumor progression while interfering with immune responses through proteins such as SREBP2, NSDHL, and STARD4.

The intricate nature of sphingolipid metabolism adds another layer of complexity. While ceramide accumulation exhibits tumor-suppressive effects by enhancing apoptosis and chemotherapy sensitization, glycosylated forms like Globo-H ceramide and GD2 are associated with tumorigenesis, angiogenesis, and cancer stem cell maintenance. Furthermore, lipid reprogramming plays a vital role in promoting epithelial-mesenchymal transition (EMT), enhancing migratory ability and drug resistance through factors like ELOVL2, SGMS2, and CXCL8.

Beyond cancer cell metabolism, the surrounding tumor immune microenvironment adapts in response to lipid cues. M2 macrophages, cancer-associated fibroblasts, and CD8+ T cells demonstrate lipid-driven phenotypic shifts that support tumor evasion and therapy failure. Standard treatments, including chemotherapy, endocrine therapy, HER2-targeted therapy, and immune checkpoint inhibitors, face significant challenges due to lipid metabolic rewiring. The upregulation of enzymes such as CD36, FASN, CPT1, and GPR120 exemplifies how tumor cells exploit lipid pathways to avoid apoptosis, reduce drug accumulation, and sustain stemness.

This comprehensive exploration reveals the intricate relationship between lipid metabolism and breast cancer progression. By targeting specific metabolic pathways, researchers aim to develop innovative strategies to overcome treatment resistance and improve patient outcomes, offering hope for more effective therapies in the future.