Abstract LB515: Cardiovascular risk assessed by aptamer-based proteomics is increased in early breast cancer

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Abstract Background: Cancer patients with a high risk for cardiovascular (CV) disease may be susceptible to cardiotoxic injury during cancer therapy. Accordingly, CV risk assessment may help in identifying candidates for preventive cardioprotective treatment. Since existing CV risk scores may lack the sensitivity and granularity to reflect the changes in CV risk that is associated with early cancer, we hypothesized that a CV risk score based on aptamer-based proteomics would permit discrimination of CV risk between patients with early breast cancer and age-, sex- and risk factor-matched healthy subjects. Moreover, we hypothesized that CV risk as assessed by aptamer-based proteomics first increases during and subsequently decreases after anthracycline-containing chemotherapy. Methods: We included 120 women with early breast cancer participating in the 2x2 factorial, randomized, placebo-controlled Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA) trial who were assigned to candesartan vs placebo and metoprolol vs placebo. Blood samples were obtained serially at: Visit 1 (ie, post-surgery but prior to epirubicin), following the first cycle of epirubicin (Visit 2), after the completion of epirubicin therapy (Visit 3), following adjuvant therapy (Visit 4), and 1-2 years after completion of adjuvant and blinded therapy (Visit 5). Age-, sex-, and risk factor-matched subjects (n = 500) from the Fenland study served as controls. We used highly multiplexed modified aptamer-based proteomics to measure ~5000 plasma proteins. A validated 27-protein CV risk model (CVD) that provides information on absolute risk of myocardial infarction, stroke, heart failure or mortality over a 4-year period was used as the dependent variable. Results: The CVD risk probability was significantly higher at Visit 1 than in the age-, sex- and risk-factor matched control group (p < 0.001). The CVD risk probability increased significantly from baseline to completion of epirubicin therapy (p < 0.001) and dropped below baseline levels for subsequent timepoints after the completion of epirubicin treatment. The mean CVD risk increased from 15.9% at Visit 2 to 24.6% at Visit 3, resulting in the percentage of subjects in the medium-high risk bin increasing from 9% at Visit 2 to 28% at Visit 3. The CVD risk distribution at the end of study was similar to the initial distribution at baseline and Visit 2. Conclusion: Using a novel CVD risk proteomics model, we observed that (1) The CVD risk of patients with early breast cancer is increased compared to age-, sex- and risk factor-matched individuals from the general population; (2) CVD risk increases during adjuvant epirubicin-containing chemotherapy, and (3) after completed adjuvant cancer therapy CVD risk returns to pre-chemotherapy level. Use of the CVD risk score may represent a novel tool to identify and monitor cancer patients who may benefit from preventive cardioprotective therapy. Citation Format: Torbjørn Omland, Jessica Chadwick, Ragnhild Røysland, Geeta Gulati, David Astling, Siri L. Heck, Victoria Vinje, Rachel Ostroff, Peter Ganz, Jürgen Geisler, Steve Williams. Cardiovascular risk assessed by aptamer-based proteomics is increased in early breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB515.