Lipid and High-Density Lipoprotein (HDL) Subfraction Changes in Premenopausal and Postmenopausal Women With Breast Cancer Receiving Hormonal Therapy

Background and aim: Hormonal modulation therapy is an important component of hormone receptor-positive breast cancer treatment. However, the type and duration of hormonal therapies have distinct effects on lipid profile parameters and cardiovascular disease risk. This study aimed to investigate the impact of tamoxifen and aromatase inhibitors (AIs) on lipid profiles and high-density lipoprotein (HDL) subfractions in women with breast cancer. Materials and methods: In this retrospective observational study, 100 women were included (50 healthy controls and 50 patients with histologically confirmed breast cancer). Among breast cancer patients, 25 were premenopausal receiving tamoxifen treatment, and 25 were postmenopausal receiving AI therapy, based on routine clinical practice. Lipid parameters were assessed at baseline and following six months of treatment in all participants. Premenopausal patients received tamoxifen, while postmenopausal patients were treated with AIs. Serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), HDL cholesterol, and HDL subfractions (HDL-2 and HDL-3) were analyzed. Results: In the tamoxifen-treated premenopausal cohort, total cholesterol decreased by 8.48% and LDL-C by 15.94%, with redistribution toward larger HDL particles, reflected by an increase in HDL-2 of 21.1% and a decrease in HDL-3 of 12.06% (all p<0.001). In the postmenopausal aromatase inhibitor cohort, a mixed lipid pattern was observed, with increases in total cholesterol (+3.38%) and LDL-C (+7.02%), decreases in HDL-C (-1.56%) and HDL-2 (-20.75%), an increase in HDL-3 (+8.69%), and a decrease in triglycerides (-10.95%) (all p<0.001). Direct comparison of change scores between cohorts showed significant differences for all examined lipid parameters (all p<0.001). Conclusion: Distinct six-month trajectories in lipid profile parameters and HDL subfractions were observed between premenopausal women receiving tamoxifen and postmenopausal women receiving aromatase inhibitors. These findings likely reflect the combined influence of endocrine therapy and underlying menopausal physiology and should not be interpreted as a direct causal head-to-head comparison of isolated drug effects.