Abstract 11697: Associations of Soluble Urokinase-Type Plasminogen Activator Receptor and Doxorubicin-Related Cardiotoxicity at Standard Treatment Doses for Breast Cancer

Abstract

Introduction: Elevated soluble urokinase type plasminogen activator (suPAR) is a risk factor for renal and cardiovascular (CV) diseases in the general population. Hypothesis: We evaluated associations between suPAR and markers of subclinical cardiotoxicity in breast cancer (BCa) patients receiving standard (std) dose doxorubicin (DOX) therapy. Methods: We conducted a prospective study of patients at Rush University Medical Center who received std (≤240 mg/m2, 4 cycles) DOX-based chemotherapy for BCa between January 2017 and May 2019. We used mixed effects linear regression models to evaluate associations between suPAR and global longitudinal strain (GLS), NT-proBNP, troponin-I, and hsCRP at baseline, cycle 2 and 4 of DOX, and 3, 6, and 12 months post-DOX treatment with adjustment for baseline demographics, CV risk factors, and CV medications. Results: Of the 37 women in our study (age 47±9.3 years, 60% White, 60% left-sided BCa, and 86% adjuvant radiation therapy), the median baseline suPAR was normal at 1.83 (1.31, 3.68) ng/dL. No woman experienced clinically significant cardiotoxicity during treatment (>10% decrease in LVEF to <50%). Baseline GLS was normal (-20.2±2.3%) and the mean change in GLS following DOX therapy was +1.1%. Neither baseline suPAR nor suPAR levels during treatment were associated with GLS, NT-proBNP, hsCRP, and troponin-I (all p<0.05). Surrogate biomarkers of cardiotoxicity such as troponin-I and hsCRP were not associated with GLS (p<0.05) while NT-proBNP was negatively associated with GLS with marginal significance (p=0.04). Conclusions: In patients receiving std DOX treatment for BCa ± radiation therapy, there was minimal subclinical cardiotoxicity as evidenced by minimal changes in GLS and lack of associations between cardiac biomarkers and GLS. Furthermore, suPAR was not associated with any of these markers at this std DOX dose for BCa. A normal baseline suPAR level may be associated with low risk for DOX-associated cardiotoxicity.