Lipid Metabolic Reprogramming in Breast Cancer: Mechanisms and Emerging Therapeutic Strategies.

Breast cancer remains the most commonly diagnosed malignancy among women worldwide, with a steadily increasing incidence. Lipid metabolic reprogramming is increasingly recognized as both a hallmark and a fundamental driver of breast cancer progression. Breast cancer cells exhibit enhanced lipid uptake, de novo fatty acid synthesis, fatty acid oxidation, and lipid storage, which collectively support membrane biosynthesis, energy production, and oncogenic signaling. In addition to cancer cell-intrinsic effects, lipid metabolic alterations reshape the tumor microenvironment by modulating immune responses, stromal activation, and angiogenesis. Key metabolic enzymes, including FASN, ACC, ACLY, SCD, and FABP4, play central roles in these processes and represent promising therapeutic targets. Emerging evidence from preclinical and clinical studies highlights the therapeutic potential of targeting lipid metabolism, particularly in aggressive subtypes such as triple-negative breast cancer. Despite these advances, challenges such as therapeutic resistance, metabolic compensation, and lack of predictive biomarkers remain major barriers to clinical translation. Overall, targeting lipid metabolic vulnerabilities offers a promising strategy for precision therapy in breast cancer.