Abstract 791: Increased aortic stiffening in premenopausal women and triple negative breast cancer patients: impact of biomarkers and breast cancer therapy- findings from the PREVENT Trial (WF-98213)

Abstract Background: Breast cancer (BC) systemic therapies have improved survival but are associated with cardiovascular (CV) risks, particularly in premenopausal women with hormone receptor-positive (HR+) BC under near-complete estrogen deprivation (NCED) and in those with triple-negative BC (TNBC) who may experience chemotherapy-induced menopause. This PREVENT Trial (NCT01988571) sub-analysis investigated the impact of BC treatment, menopausal status, and biomarkers on vascular stiffness over two years. Methods: This randomized trial included 238 BC patients receiving either atorvastatin (40 mg/day) or placebo for two years (PREVENT Trial WF-98213 Wake Forest NCORP Research Base UG1CA189824, ECOG-ACRIN and Alliance). Aortic pulse wave velocity (PWV) and aortic distensibility (AoD), measured via cardiac magnetic resonance imaging (CMR), were assessed at baseline, 6 months, and 24 months as indicators of vascular stiffness. Longitudinal general linear mixed models adjusted for baseline values, hypertension, body mass index, BC subtype, menopausal status, and statin treatment group evaluated changes in vascular stiffness. Univariate adjustments were performed to assess the influence of biomarkers, including cholesterol, aldosterone, renin, IL-6, TNF-alpha, and CRP. Results: Of 238 participants, 116 were premenopausal (65% HR+, 35% TNBC) and 122 postmenopausal (58% HR+, 42% TNBC). At baseline, PWV did not differ significantly between BC subtypes but by 24 months, TNBC patients exhibited significantly increased PWV (p = 0.0298). Premenopausal women, despite having lower baseline PWV, surpassed postmenopausal levels by 24 months. AoD declined significantly across all subgroups (p < 0.05), reflecting increased vascular stiffening. Preliminary analysis links biomarkers with vascular stiffness. In TNBC patients, every 1 ng/mL increase in renin is associated with a 0.18 mmHg-1 AoD decrease at 6 months (p=0.0343). For IL-6, every 5 pg/mL increase is linked to a 0.145 mmHg-1 AoD increase at 6 months and 0.192 mmHg-1 at 24 months in TNBC and postmenopausal women (p=0.0288 and p=0.0325, respectively). For cholesterol, every 10 mg/dL rise in TNBC reduces AoD by 0.261 mmHg-1, reflecting higher PWV (p=0.0298). Statin treatment did not mitigate aortic stiffening. Conclusions: This study reveals that premenopausal and TNBC women undergoing anthracycline-based chemotherapy exhibit significant increases in vascular stiffness, highlighting their heightened CV risk. Biomarker interactions differed across subgroups, with renin and cholesterol linked to poorer vascular outcomes in TNBC patients, while IL-6 appeared to promote compensatory vascular remodeling in TNBC patients and postmenopausal women. Enhanced cardiac monitoring and targeted interventions may be essential for these high-risk populations. Citation Format: Lorraine N. Vélez-Torres, Alexandra Thomas, Sarah Hatcher, Ralph B. D'Agostino, Nathaniel S. O'Conell, Carolyn J. Park, W Gregory Hundley, Jennifer H. Jordan. Increased aortic stiffening in premenopausal women and triple negative breast cancer patients: impact of biomarkers and breast cancer therapy- findings from the PREVENT Trial (WF-98213) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 791.