The impact of body composition on cardiac function in women with early breast cancer taking cardiotoxic chemotherapy.

Abstract

12021 Background: Anthracyclines and HER2-directed therapies have improved survival in early breast cancer (EBC), but cardiotoxicity remains a concern for long-term survivors. Cardiovascular disease may ultimately exceed breast cancer as a cause of death, highlighting the need for better understanding of therapy-related cardiac dysfunction. Body composition abnormalities are linked to adverse cardiovascular outcomes but are not well captured by body mass index are understudied. We evaluated longitudinal associations between baseline CT-derived body composition and echocardiography measures of cardiac structure and function. Methods: This is a retrospective analysis of women with stage I–III EBC treated with anthracyclines and/or trastuzumab at the University of Pennsylvania. Eligible patients had a pre-treatment and ≥1 follow-up echocardiogram and pre-treatment abdominal CT or PET-CT imaging for body composition assessment. L3-based segmentation quantified skeletal muscle mass, muscle density (SMD), subcutaneous and visceral adiposity (SAT, VAT), and adipose tissue density (SATD, VATD). Core-lab echocardiographic outcomes included systolic function (LVEF, GLS) and diastolic function (E/e′). Using multivariable-adjusted generalized estimating equations (GEE) models, we evaluated longitudinal associations between baseline body composition (per 1-SD increase) and two complementary outcomes for each metric: (1) absolute values over time (overall burden) and (2) change from baseline (within-participant worsening). Results: Across 182 participants, the median age was 49.5 years (Q1-Q3 41–60), HER2-positive disease was present in 64 (35.4%), estrogen receptor–positive disease in 114 (62.6%), and triple-negative disease in 37 (20.4%). Anthracycline-based therapy was administered to 150 (82.4%), radiation therapy to 140 (76.9%), and mastectomy was performed in 106 (58.6%). Baseline hypertension, hyperlipidemia, and diabetes were present in 56 (30.8%), 43 (23.6%), and 12 (6.6%), respectively. In multivariable-adjusted GEE models, higher baseline VAT was associated with a greater decline in LVEF over time (−2.1 LVEF points per 1-SD increase; 95% CI −4.1 to −0.1; p=0.04). We next evaluated diastolic function, where higher baseline VAT was associated with a greater increase in E/e′ over time (β 0.38 per 1-SD increase; 95% CI, 0.01 to 0.74; p=0.04). In models evaluating absolute E/e′ over time, higher VAT (β 0.51; 95% CI, 0.11 to 0.91) and SAT (β 0.37; 95% CI, 0.06 to 0.59), and lower SMD (β −0.34; 95% CI, −0.66 to −0.02) and VAT density (β −0.36; 95% CI, −0.67 to −0.05) were associated with higher E/e′. No adjusted associations were observed for longitudinal change in GLS (all p>0.05). Conclusions: Baseline visceral adiposity was associated with worsening in longitudinal changes in systolic and diastolic function during cardiotoxic breast cancer therapy.