Biomarkers for Presymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients

Abstract

Cardiotoxicity of doxorubicin (DOX) remains an important health concern. DOX cardiotoxicity is cumulative-dose-dependent and begins with the first dose of chemotherapy. No biomarker for presymptomatic detection of DOX cardiotoxicity has been validated. Our hypothesis is that peripheral blood cells (PBC) gene expression induced by the early doses of DOX-based chemotherapy could identify potential biomarkers for presymptomatic cardiotoxicity in cancer patients. PBC gene expression of 33 breast cancer patients was conducted before and after the first cycle of DOX-based chemotherapy. Cardiac function was evaluated before the start of chemotherapy and at its completion. Differentially expressed genes (DEG) of patients who developed DOX-associated cardiotoxicity after the completion of chemotherapy were compared with DEG of patients who did not. Ingenuity database was used for functional analysis of DEG. Sixty-sevens DEG (P<0.05) were identified in PBC of patients with DOX-cardiotoxicity. Most of DEG encode proteins secreted by activated neutrophils. The functional analysis of the DEG showed enrichment for immune- and inflammatory response. This is the first study to identify the PBC transcriptome signature associated with a single dose of DOX-based chemotherapy in cancer patients. We have shown that PBC transcriptome signature associated with one dose of DOX chemotherapy in breast cancer can predict later impairment of cardiac function. This finding may be of value in identifying patients at high or low risk for the development of DOX cardiotoxicity during the initial doses of chemotherapy and thus to avoid the accumulating toxic effects from the subsequent doses during treatment.

Update on pathophysiology and preventive strategies of anthracycline‐induced cardiotoxicity

“…Blood cardiac biomarkers are used to identify cardiotoxicity while receiving therapy. Increases in cardiac troponins reflect myocardial injury, and chronic increases in natriuretic peptides indicate ventricular wall stress . Both represent an effective method for monitoring cardiac status, and identifying patients who may benefit from early medical intervention.…”

Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients

“…[9,10] The other was a prospective observational study investigating doxorubicin toxicity in breast-cancer patients who followed the same neoadjuvant chemotherapy regimen as the Phase II trial, but without the addition of bevacizumab; these patients were enrolled between 12/16/2010 and 9/1/2013. [11] Both studies were conducted at the University of Arkansas for Medical Sciences, and both had IRB approval. Serial blood samples were collected at baseline and at each visit from patients in both studies.…”

Recent advances in cardio‐oncology: a report from the ‘Heart Failure Association 2019 and World Congress on Acute Heart Failure 2019’

“…71 Combined measurements of N-terminal pro B-type natriuretic peptide as markers of CV overload and troponins for myocardial injury during cancer therapy may be useful. 73 Professor Radek Pudil (Hradec Kralove, Czech Republic) and Dr Kalliopi Keramida, (Athens, Greece) talked about different prevention strategies in order to minimize the development of CTRCM. 73 Professor Radek Pudil (Hradec Kralove, Czech Republic) and Dr Kalliopi Keramida, (Athens, Greece) talked about different prevention strategies in order to minimize the development of CTRCM.…”

“…72 Lastly, microRNA were discussed as potential new biomarkers in cardiooncology. 73 Professor Radek Pudil (Hradec Kralove, Czech Republic) and Dr Kalliopi Keramida, (Athens, Greece) talked about different prevention strategies in order to minimize the development of CTRCM. The proposed approach consists of three different intervention phases according to the implementation of anti-cancer treatment.…”