Back to Search Start Over

Paraoxonase-1 Activity in Breast Cancer Patients Treated With Doxorubicin With or Without Trastuzumab

Paraoxonase-1 Activity in Breast Cancer Patients Treated With Doxorubicin With or Without Trastuzumab

Authors :
Elizabeth W. Thompson
Biniyam G. Demissei
Amanda M. Smith
Priya Brahmbhatt
Jessica Wang
Amy Clark
Angela DeMichele
Vivek Narayan
Payal Shah
Lova Sun
Benedicte Lefebvre
Michael G. Fradley
Joseph R. Carver
W.H. Wilson Tang
Bonnie Ky
Source :
JACC: Basic to Translational Science
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

Visual Abstract<br />Highlights • PON-1 is an HDL-associated cardioprotective enzyme that prevents oxidized-LDL formation and has not previously been studied in cardio-oncology. • To determine the associations between PON-1 and the development of CTRCD, the Pon and Aryl serum enzymatic activity levels of PON-1 were quantified in a cohort of 225 patients with breast cancer receiving doxorubicin with or without trastuzumab. • After doxorubicin completion, the activity levels of both Pon and Aryl were significantly decreased. • Early increases in the Pon enzymatic activity of PON-1 were associated with increased risk of CTRCD. • With further study, PON-1 activity may provide insight into mechanistic risk prediction of CTRCD with doxorubicin chemotherapy.<br />Summary The objective of this study was to determine associations of paraoxonase-1 (PON-1) with development of cancer therapy–related cardiac dysfunction (CTRCD). PON-1 is a cardioprotective enzyme associated with high-density lipoprotein that prevents oxidized low-density lipoprotein formation. Given the role of oxidative stress in doxorubicin-induced cardiotoxicity, PON-1 activity may have relevance for the prediction of CTRCD. In 225 patients with breast cancer receiving doxorubicin with or without trastuzumab, we quantified PON-1 activity through its paraoxonase (Pon) and arylesterase (Aryl) enzymatic activity at baseline, during, and after doxorubicin completion. Echocardiograms were performed at baseline, during therapy, and annually. CTRCD was defined as a decrease in left ventricular ejection fraction by ≥10% from baseline to

Details

ISSN :
2452302X
Volume :
7
Database :
OpenAIRE
Journal :
JACC: Basic to Translational Science
Accession number :
edsair.doi.dedup.....2dadd34a04c67d94c46bd9d5fb98d63f
Full Text :
https://doi.org/10.1016/j.jacbts.2021.10.010