Abstract PO5-15-01: Prospective Biomarker Assessment of Cardiotoxicity Among Ethnically Diverse Women with Early Breast Cancer

Abstract

Abstract Background: Approximately 4.1 million women in the United States are living with breast cancer1. Cardiac dysfunction is a significant adverse effect of commonly used breast cancer therapies like doxorubicin (D) and trastuzumab (T). The cardiotoxicity (CTox) associated with these agents manifests as a reduction in left ventricular ejection fraction (LVEF) with or without signs and symptoms of heart failure. Purpose: The objective of this study is to evaluate serum cardiac and inflammatory biomarkers over time and their association with CTox development. Methods: A total of 133 newly diagnosed stage I-III invasive breast cancer patients were enrolled in a prospective clinical trial (2013-2017) and received standard of care T and/or D based systemic therapy. They underwent serial echocardiograms every 6 months for two years and then based on clinical need for a total of six years. CTox was defined as a >10% drop in LVEF, and/or LVEF < 50%. Biomarker data was collected at baseline, 12 and 24 months and included both cardiac biomarkers (Troponin-I, TN-I and amino terminal B-type natriuretic peptide, NT-proBNP) and measures of inflammation (C-reactive protein, CRP). Of the 32 with CTox patients, 15 had adequate serum samples and were matched with 15 patients without CTox (N=30), controlling for age, race, and treatment regimen prior to serum sample analysis. Results: The mean LVEF at baseline was similar between CTox and non-CTox patients (64% vs 62%, p=0.342). However, over the course of 12 and 24 months, CTox patients experienced a statistically significant decrease in LVEF compared to their baseline values (55% and 56%, respectively, p < 0.001). At baseline, CTox patients had higher CRP levels compared to non-CTox (13.4 mg/L vs 3.35 mg/L), however this difference did not reach statistical significance (P >0.05). Although this difference seemed to narrow at 12 months (3.88 mg/L vs 1.52 mg/L, p< 0.05) and 24 months (6.85 mg/L vs 2.36 mg/L, p< 0.05), CTox patients consistently had higher mean CRP levels. Mean TN-I levels increased at both 12 and 24 months compared to baseline (CTox 1.13 ng/L, 7.13 ng/L, 4.13 ng/L vs non-CTox 0.800 ng/L, 8.13 ng/L, 4.60 ng/L, p< 0.05) but there were no significant differences between the two groups (p >0.05). While baseline NT-proBNP levels did not differ significantly between the CTox and non-CTox patients, there were statistically significant increases in CTox patients at 12 and 24 months (205 pg/mL vs 74 pg/mL, and 200 pg/mL vs 96 pg/mL, p < 0.01, respectively). Conclusion: In a well characterized, diverse, matched subset of patients with early breast cancer who were prospectively followed with serial echocardiograms, distinct biomarker patterns were observed. Measures of inflammation (CRP) at baseline were different and these changes appeared to diminish over time. While the cardiac biomarker TN-I appeared to increase in both +CTox and -CTox group over time, only those with differential NT-proBNP elevations were associated with cardiotoxicity. 1Lisa Gallicchio, PhD and others, Estimation of the Number of Individuals Living With Metastatic Cancer in the United States, JNCI: Journal of the National Cancer Institute, Volume 114, Issue 11, November 2022, Pages 1476–1483 Citation Format: Shahzaad Jahangier, Rubina Qamar, Maharaj Singh, Vinay Thohan, James Weese, Bijoy Khandheria, Anna Kamke-Jordan. Prospective Biomarker Assessment of Cardiotoxicity Among Ethnically Diverse Women with Early Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-15-01.