Lipid Profiles in Breast Cancer: Clinical Associations and Biological Insights

Alterations in lipid metabolism are increasingly recognized as important contributors to breast cancer biology. Lipids regulate membrane structure, intracellular signaling, and energy homeostasis, and cancer cells undergo lipid metabolic reprogramming to support tumor growth and progression. This narrative review summarizes current evidence on the relationship between circulating lipid profiles and breast cancer risk, tumor characteristics, and outcomes, with a focus on total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), as well as the effects of endocrine therapies on lipid metabolism. Epidemiological studies show heterogeneous and lipid-specific associations that vary by menopausal status, tumor subtype, and study design. Triglycerides and LDL-C are most consistently linked to aggressive tumor features and disease progression, whereas total cholesterol appears to reflect broader metabolic and hormonal disturbances rather than a direct causal role. HDL-C shows inconsistent associations, likely due to functional heterogeneity not captured by circulating HDL-C levels alone. Mechanistic studies support a role for lipid metabolism in promoting tumor growth, invasion, angiogenesis, and therapy resistance. Endocrine therapies further modify lipid profiles, with tamoxifen generally reducing total cholesterol and LDL-C while increasing triglycerides, and aromatase inhibitors showing largely neutral effects in recent population-based studies. Overall, circulating lipid fractions are not suitable as standalone biomarkers but may provide clinically relevant information when interpreted in the context of tumor biology, metabolic health, and long-term survivorship care.