Abstract 11619: Topoisomerase 2ß Expression in Peripheral Blood Predicts Susceptibility to Anthracycline-Induced Cardiomyopathy
Objective: Anthracycline-induced cardiotoxicity was recently shown to be mediated by Topoisomerase 2β (Top2β). Deletion of Top2β from murine cardiomyocytes prevents anthracycline-induced cardiotoxicity. We hypothesized that patients with high Top2β expression level should be more sensitive to anthracycline. Here, we tested whether Top2β expression in peripheral blood can be used as a surrogate biomarker for anthracycline susceptibility.
Methods: Two groups of patients were enrolled in the study. Anthracycline-sensitive group was defined as patients who received cumulative equivalent dose of doxorubicin < 250 mg/m2 and had decrease in ejection fraction (EF) ≥ 10% from baseline and below 50% after exposure to anthracycline. Anthracycline-resistant group was defined as patients who received cumulative equivalent dose of doxorubicin > 450 mg/m2 and had preserved EF. Epirubicin and idarubicin were converted to the equivalent of doxorubicin dose using a conversion factor of 0.5 and 2, respectively. Top2β levels in peripheral blood of patients were determined by enzyme-linked immunosorbent assay.
Results: 36 patients were enrolled. There was no statistical difference between these two groups in terms of age, sex, and risk factors, such as hypertension, diabetes, dyslipidemia, and radiation exposure. All patients in the anthracycline-resistant group (n=15) had Top2β levels below a cut-point of 0.5 ng/μg. Top2β levels in the anthracycline-sensitive group (n=21) were significantly higher than the resistant group (0.4±0.28 vs. 0.23±0.1, p=0.026). Five anthracycline-sensitive patients had Top2β levels greater than 0.5 ng/μg. 14 anthracycline-sensitive patients with Top2b levels less than 0.5 ng/μg had confounding factors, such as CAD, sepsis, herceptin treatment, and hypertensive cardiomyopathy.
Conclusion: Patients with Top2β levels above 0.5 ng/μg are at a higher risk for developing anthracycline-induced cardiotoxicity.
- © 2013 by American Heart Association, Inc.