Format

Send to

Choose Destination
J Am Heart Assoc. 2017 Nov 8;6(11). pii: e006513. doi: 10.1161/JAHA.117.006513.

Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study.

Author information

1
Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
2
Center for Heart Failure Research, University of Oslo, Norway.
3
Department of Oncology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
4
Institute of Clinical Medicine, University of Oslo, Norway.
5
Department of Cardiology, Division of Cardiovascular and Pulmonary Diseases, Oslo University Hospital, Ullevål, Oslo, Norway.
6
Section for Medical Biochemistry, Division for Diagnostics and Technology, Akershus University Hospital, Lørenskog, Norway.
7
Clinic for Medical Diagnostics, Vestre Viken Hospital Trust, Drammen, Norway.
8
Department of Breast and Endocrine Surgery, Division of Surgery, Akershus University Hospital, Lørenskog, Norway.
9
Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway torbjorn.omland@medisin.uio.no.

Abstract

BACKGROUND:

Anthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on-treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines.

METHODS AND RESULTS:

This report encompasses 121 women included in the 2×2 factorial, placebo-controlled, double-blind PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial with metoprolol and candesartan given concomitantly with anticancer therapy containing the anthracycline, epirubicin (total cumulative dose, 240-400 mg/m2). Cardiovascular magnetic resonance, echocardiography images, and circulating levels of biomarkers were obtained before and after anthracycline treatment. Cardiac troponins I and T, B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide, C-reactive protein, and galectin-3 increased during anthracycline therapy (all P<0.05). The troponin response was attenuated by metoprolol (P<0.05), but not candesartan. There was no association between change in biomarker concentrations and change in cardiac function during anthracycline therapy.

CONCLUSIONS:

Treatment with contemporary anthracycline doses for early breast cancer is associated with increase in circulating cardiovascular biomarkers. This increase is, however, not associated with early decline in ventricular function. Beta-blockade may attenuate early myocardial injury, but whether this attenuation translates into reduced risk of developing ventricular dysfunction in the long term remains unclear.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrial.gov. Unique identifier: NCT01434134.

KEYWORDS:

C‐reactive protein; beta‐blocker; brain natriuretic peptide; cardio‐oncology; magnetic resonance imaging; troponin

PMID:
29118031
PMCID:
PMC5721750
DOI:
10.1161/JAHA.117.006513
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central Icon for Norwegian BIBSYS system
Loading ...
Support Center