ACC 2020: Potential Biomarker of Cardiac Dysfunction in Patients Treated for Breast Cancer
Posted: Tuesday, April 14, 2020
According to Bonnie Ky, MD, and colleagues from the University of Pennsylvania, Philadelphia, paraoxonase-1, a cardioprotective enzyme associated with high-density lipoprotein, may act as a novel predictive biomarker for cancer therapy–related cardiac dysfunction in patients with breast cancer treated with doxorubicin alone or with trastuzumab. The results were presented at the virtual 2020 American College of Cardiology (ACC) World Congress of Cardiology (Abstract 1015-05) and published in the Journal of the American College of Cardiology. Researchers indicate that patients who achieved declines in levels of paraoxonase and lactonase enzymes after doxorubicin treatment may have a lower risk of cancer therapy–related cardiac dysfunction.
“There is an ongoing need for mechanistic biomarkers to help enhance the understanding of pathophysiologic mechanisms and facilitate the early detection and prediction of cancer therapy–related cardiac dysfunction,” the researchers stated.
The investigators assigned 225 patients with breast cancer to receive doxorubicin, alone or with trastuzumab. To analyze paraoxonase-1 activity, paraoxonase, arylesterase, and lactonase enzymatic activity levels were measured at baseline, after 1 month, and at treatment completion. The study defined cancer therapy–related cardiac dysfunction as a decrease in left ventricular ejection fraction by at least 10% from baseline to less than 50%.
Baseline paraoxonase and lactonase levels were independently associated with factors including black race and worse disease stage. After doxorubicin treatment, the enzymatic activity levels of all three enzymes decreased. Following doxorubicin treatment, decreased paraoxonase or lactonase levels from baseline were associated with a lower risk of cardiac dysfunction (hazard ratios: paraoxonase = 0.23; lactonase = 0.10). Although the mechanistic understanding of these findings is unknown, the team hypothesized that decreases in activity may reflect less oxidative stress. The researchers noted that more studies are necessary to validate their study results.
Disclosure: The study authors reported no conflicts of interest.
