Heart Failure in Breast Cancer Survivors: Focus on Early Detection and Novel Biomarkers.

PURPOSE OF REVIEW: Breast cancer survival rate has greatly improved in the last two decades due to the emergence of next-generation anti-cancer agents. However, cardiotoxicity remains a significant adverse effect arising from traditional and emerging chemotherapies as well as targeted therapies for breast cancer patients. In this review, we will discuss cardiotoxicities of both traditional and emerging therapies for breast cancer. We will discuss current practices to detect cardiotoxicity of these therapies with the focus on new and emerging biomarkers. We will then focus on 'omics approaches, especially the use of epigenetics to discover novel biomarkers and therapeutics to mitigate cardiotoxicity. RECENT FINDINGS: Significant cardiotoxicities of conventional chemotherapies remain and new and unpredictable new forms of cardiac and/or vascular toxicity emerge with the surge in novel and targeted therapies. Yet, there is no clear guidance on detection of cardiotoxicity, except for significant left ventricular systolic dysfunction, and even then, there is no uniform definition of what constitutes cardiotoxicity. The gold standard for detection of cardiotoxicity involves a serial echocardiography in conjunction with blood-based biomarkers to detect early subclinical cardiac dysfunction. However, the ability of these tests to detect early disease remains limited and not all forms of toxicity are detectable with these modalities. There is an unprecedented need to discover novel biomarkers that are sensitive and specific for early detection of subclinical cardiotoxicity. In that space, novel echocardiographic techniques, such as strain, are becoming more common-place and new biomarkers, discovered by epigenetic approaches, seem to become promising alternatives or adjuncts to conventional non-specific cardiac biomarkers.

Successful immune checkpoint inhibitor rechallenge after immune-related pericarditis: Clinical case series.

Pericardial diseases secondary to immune checkpoint inhibitors (ICI) are rare. Here, we describe two cases of immune-related pericarditis caused by ICI for treatment of advanced NSCLC. Select patients can be successfully rechallenged with ICI after immune-related pericardial disease.

Factors Associated with Adverse Cardiovascular Events in Cancer Patients Treated with Bevacizumab.

Background: Bevacizumab, a vascular endothelial growth factor (VEGF) monoclonal antibody commonly used for the treatment of various cancers, is often associated with adverse cardiovascular effects such as hypertension, cardiac and cerebral ischemia, thrombosis, and bleeding events. Factors associated with increased risks of adverse cardiovascular effects with bevacizumab have not been intensively studied. In this study, we determined factors associated with hospital admissions due to cardiovascular complications in patients who received bevacizumab for cancer treatment. Methods and Results: We retrospectively collected data for all patients treated with bevacizumab between the 1st January 2016 and the 31st December 2017 at the Hunter New England Local Health District. Patients' characteristics and their medical history were obtained from hospital electronic medical records. Outcome data were sourced from the Institutional Cardiac and Stroke Outcomes Unit database. A total of n = 230 patients (mean age 65, males n = 124 (53.9%)) were treated with bevacizumab during the study period. N = 28 patients were admitted to hospital for a major cardiovascular-related event. Higher total treatment dose (p < 0.05), concomitant hypertension (p = 0.005), diabetes (p = 0.04), atrial fibrillation (p = 0.03), and lack of use of statin therapy (p = 0.03) were key contributors to hospital admission. Conclusions: Results of our study highlight the fact that patients with concomitant baseline cardiovascular disease/risk factors are at an increased risk of cardiovascular hospitalization related to bevacizumab treatment. Careful baseline cardiovascular assessment may be an essential step to minimize cardiovascular complications.

Hypercalcaemia due to Sarcoidosis during Treatment with Avelumab for Metastatic Merkel Cell Carcinoma.

Merkel cell carcinoma is a rare but aggressive skin cancer. Response to chemotherapy is not durable but avelumab, an anti-PD-L1 inhibitor, showed promising ongoing response in a phase II trial. Checkpoint inhibitors including avelumab are known to cause overactivation of the immune system, leading to immune-related adverse events (irAE). We describe the first reported case of hypercalcaemia secondary to reactivation of sarcoidosis in a patient with metastatic Merkel cell carcinoma on avelumab. Hypercalcaemia was managed with corticosteroids to full resolution and avelumab therapy was safely continued.