Baseline dyslipidemia in treatment-naïve breast cancer: Molecular subtype–specific patterns in a large cohort.

Abstract

e12692 Background: Cardiovascular disease has emerged as a major cause of long-term morbidity and mortality among breast cancer survivors. However, cardiometabolic risk profiles present at the time of breast cancer diagnosis—prior to any anticancer therapy—remain incompletely characterized, particularly across molecular subtypes. Evidence from large, real-world cohorts evaluating baseline dyslipidemia in treatment-naïve patients is limited. We aimed to characterize the prevalence and subtype-specific patterns of dyslipidemia at diagnosis in women with newly diagnosed breast cancer. Methods: We conducted a retrospective cohort study of 5,246 women with pathologically confirmed, treatment-naïve breast cancer diagnosed between 2014 and 2024. All clinical characteristics, laboratory measurements, and electrocardiographic data were collected at diagnosis before surgery or systemic therapy. Molecular subtypes were classified as Luminal A, Luminal B (HER2−), Luminal B (HER2+), HER2-enriched, and triple-negative breast cancer (TNBC) according to ASCO/CAP guidelines based on immunohistochemistry and in situ hybridization results. Dyslipidemia was defined as abnormal levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, or triglycerides using guideline-based lipid thresholds. Subtype-specific comparisons were performed, and multivariable logistic regression analyses were used to identify factors associated with dyslipidemia. Results: Overall, 54.1% of patients exhibited dyslipidemia at diagnosis, with significant heterogeneity across molecular subtypes (P < 0.001). The prevalence was highest in Luminal A tumors (59.2%) and lowest in Luminal B (HER2−) tumors (43.9%). Elevated total cholesterol (29.5%) and triglycerides (25.7%) were the most common lipid abnormalities, while abnormalities in LDL-C and HDL-C demonstrated marked subtype-specific variation. Notably, patients with advanced-stage TNBC showed a particularly high prevalence of elevated LDL-C. In multivariable analyses, intravascular tumor thrombus was independently and consistently associated with dyslipidemia across all molecular subtypes (P < 0.001). Age and lymph node metastasis demonstrated subtype-dependent associations with dyslipidemia. Conclusions: More than half of women with newly diagnosed, treatment-naïve breast cancer present with dyslipidemia at diagnosis, with distinct patterns across molecular subtypes. These findings highlight the presence of clinically relevant cardiometabolic risk before initiation of anticancer therapy and support early lipid assessment as part of baseline cardio-oncology risk stratification. Incorporating lipid profiling at diagnosis may inform personalized survivorship planning, particularly for high-risk subtypes such as TNBC.