Risk factors of trastuzumab-induced cardiotoxicity in breast cancer

Abstract

Background:Trastuzumab targets the human epidermal growth factor receptor 2 oncogene and in combination with first-line therapy results in significantly improved survival outcomes and has thus become standard of care in both adjuvant and metastatic settings. While it is estimated that 1% to 4% of patients treated with trastuzumab will develop heart failure and ∼10% will experience a reduction in left ventricular ejection fraction (LVEF), the patient risk factors associated with trastuzumab-induced cardiotoxicity (TIC) are unclear. This meta-analysis aims to consolidate previously published data to identify the risk factors most likely leading to TIC.Methods:A search of the MEDLINE literature database using the keywords trastuzumab/Herceptin, risk factors, outcomes, cardiac, cardiotoxicity, cardiomyopathy, LVEF, and chemotherapy was performed. Only prospective/retrospective human studies were included, with additional studies excluded if they reported baseline LVEF > 68%, a cohort of <50 patients, or results that were not stratified based on cardiotoxic events. Pooled odds ratio (OR) and 95% confidence interval (CI) for each potential risk factor were calculated, with heterogeneity of data and samples explored using random-effects modeling.Results:Data were collected from 17 articles, capturing 6527 patients. Hypertension (OR 1.61, 95% CI 1.14–2.26; P < 0.01), diabetes (OR 1.62; 95% CI 1.10–2.38; P < 0.02), previous anthracycline use (OR 2.14; 95% CI 1.17–3.92; P < 0.02), and older age (P = 0.013) were all shown to be associated with TIC.Conclusion:Cardiac performance should be closely monitored in women treated with trastuzumab. Recognizing potential risk factors along with careful attention to symptoms/LVEF measurements could minimize the occurrence of TIC in this population.

Heart dose linked with cardiac events and overall survival in lung cancer radiotherapy

“…Cardiotoxicity is a serious side effect which is already found in both cytostatic and molecularly targeted therapies. [ 35 , 36 ] Meanwhile, RIHD also has long been recognized. It usually includes pericardial disease, myocardial fibrosis, ischemic heart disease, valvular disease, arrhythmias, autonomic changes, and cardiomyopathy.…”

Strategies to Prevent Cardiovascular Toxicity in Breast Cancer: Is It Ready for Primetime?

“…As hyperlipidemia has been implicated in promoting cardiac inflammation, cancer patients, like all patients, should receive standard risk assessment based on the 2019 American College of Cardiology/American Heart Association (ACC/AHA) primary prevention guidelines to see if they would benefit from lipid lowering therapy [27,30]. Diabetes is another major risk factor which has been shown to increase the risk of cancer treatment-related cardiotoxicity in several studies, and it is critical to optimize management at the initiation of cancer therapy [27,31,32]. A few studies have suggested that genetic components may impact a patient's susceptibility to developing cancer therapy-related cardiac dysfunction.…”

Long-term cardiovascular health in adult cancer survivors

“…A recent meta-analysis of almost 30,000 women treated with trastuzumab reported an incidence for severe cardiotoxicity of 3% (95%CI 2.41-3.64) at three year follow-up [51]. Older age, a history of anthracycline administration, hypertension, obesity and diabetes are risk factors for trastuzumab-induced LV dysfunction [64,65].…”