Changes in blood metabolomes as potential markers for severity and prognosis in doxorubicin-induced cardiotoxicity: a study in HER2-positive and HER2-negative breast cancer patients.

Abstract

BACKGROUND:

We aimed to compare the changes in blood metabolomes and cardiac parameters following doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients. Additionally, the potential roles of changes in blood metabolomes as severity and prognostic markers of doxorubicin-induced cardiotoxicity were determined.

METHODS:

HER2-positive (n = 37) and HER2-negative (n = 37) breast cancer patients were enrolled. Cardiac function assessment and blood collection were performed at baseline and 2 weeks after completion of doxorubicin treatment in all patients, as well as at three months after completion of doxorubicin treatment in HER2-negative breast cancer patients. Blood obtained at all three-time points was processed for measuring cardiac injury biomarkers. Blood obtained at baseline and 2 weeks after completion of doxorubicin treatment were also processed for measuring systemic oxidative stress and 85 metabolome levels.

RESULTS:

Cardiac injury and systolic dysfunction 2 weeks after completion of doxorubicin treatment were comparable between these two groups of patients. However, only HER2-negative breast cancer patients exhibited increased systemic oxidative stress and cardiac autonomic dysfunction at this time point. Moreover, 33 and 29 blood metabolomes were altered at 2 weeks after completion of doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients, respectively. The changes in most of these metabolomes were correlated with the changes in cardiac parameters, both at 2 weeks and 3 months after completion of doxorubicin treatment.

CONCLUSIONS:

The changes in blood metabolomes following doxorubicin treatment were dependent on HER2 status, and these changes might serve as severity and prognostic markers of doxorubicin-induced cardiotoxicity.

TRIAL REGISTRATION:

The study was conducted under ethical approval from the Institutional Review Board of the Faculty of Medicine, Chiang Mai University (Registration number: MED-2563-07001; Date: April 28, 2020). The study also complied with the Declaration of Helsinki.

• Authors: Chanisa Thonusin, Nichanan Osataphan, Krit Leemasawat, Wichwara Nawara, Sirawit Sriwichaiin, Siriporn Supakham, Siriluck Gunaparn, Nattayaporn Apaijai, Areewan Somwangprasert, Arintaya Phrommintikul, Siriporn C Chattipakorn, Nipon Chattipakorn
• Journal: Journal of translational medicine (J Transl Med) Vol. 22 Issue 1 Pg. 398 (Apr 29 2024) ISSN: 1479-5876 [Electronic] England
• PMID: 38685030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2024. The Author(s).

Chemical References

• Doxorubicin
• Receptor, ErbB-2
• ERBB2 protein, human
• Biomarkers

Topics

• Humans
• Breast Neoplasms (drug therapy, blood)
• Female
• Doxorubicin (adverse effects)
• Receptor, ErbB-2 (metabolism, blood)
• Metabolome
• Middle Aged
• Prognosis
• Cardiotoxicity (blood)
• Oxidative Stress (drug effects)
• Biomarkers (blood, metabolism)
• Adult