Detecting early onset of chemotherapy‐related cardiac dysfunction in breast cancer patients in the West Virginian population using a novel panel of biomarkers

Abstract

BackgroundCardiotoxicity has been intricately linked in breast cancer patients receiving anthracyclines therapy in the clinical setting. The cumulative line of evidence has demonstrated that cardiotoxic manifestation associated with breast cancer treatment increases patients’ susceptibility to myocardial injury, reduction in left ventricular ejection fraction and complications associated with heart failure. There is currently no standardized, minimally invasive, cost effective and clinically verified procedure to monitor cardiotoxicity post‐anthracycline therapy initiation, and to detect early onset of irreversible cardiovascular complications. An important role of altered levels of serum biomarkers and circulating miRNAs have been implicated in modulating cardiac vasculature and cardiac damage.HypothesisThis study aims to create a panel of novel biomarkers and circulating miRNAs associated with cardiotoxicity, to assess the correlation between anthracycline agents and development of cardiac dysfunction, which will allow to monitor and detect early‐onset of chemotherapy related cardiac dysfunction.Materials and MethodsA total of 17 female patients with a clinical diagnosis of invasive ductal carcinoma were enrolled for the study. Blood was withdrawn and echocardiography assessment was performed at baseline (prior to initiation of anthracyclines), 3months and 6months post‐initiation of anthracycline agents. Subsequently, a total of 17 healthy controls were also recruited for the study without any form of cancer or cardiovascular complications. Enzyme Linked Immunosorbent Assays (ELISA) were performed for biomarker analysis and RT‐PCR was performed for expression of circulating miRNA levels.ResultsOur results showed that interleukin‐6 (IL‐6), matrix metalloproteinase ‐2 (MMP2) and ‐9 (MMP9), myeloperoxidase (MPO) and topoisomerase II beta (TOP2B) were significantly upregulated in serum obtained at 3months and 6months study interval post anthracycline initiation, as compared to baseline and healthy controls (p<0.01). The circulating levels of miR‐34a, miR‐208b, miR‐126, miR‐150, miR‐423 and miR‐499a were positively correlated and showed elevated levels at 3months and even higher in 6months study interval, while levels of miR‐29a were reduced at 3months, and much lower at 6months, as compared to control group (p<0.01). Assessment of echocardiographic measurements exhibited greater extent of cardiac dysfunction at 3months and 6month study interval.ConclusionOur results support the clinical application of these serum biomarkers and circulating miRNAs to develop a panel for early diagnosis of chemotherapy related cardiac dysfunction which will enable early detection of disease progression and management of irreversible cardiac damage.Support or Funding InformationThis work was supported by the Brickstreet Foundation (J.I.S.).