Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Prevention, Monitoring, and Management of Cardiac Dysfunction in Patients with Metastatic Breast Cancer

“…The HER2/neu receptor antagonist trastuzumab is indicated for the treatment of HER2‐positive breast cancer, as (neo)adjuvant therapy and for metastatic disease . Trastuzumab has also been associated with subclinical and clinical cardiac failure, with the greatest risk when administered concurrently with anthracyclines . The pivotal study of trastuzumab in advanced breast cancer showed rates of cardiac dysfunction between 13% (trastuzumab plus paclitaxel) and 27% (trastuzumab plus anthracycline and cyclophosphamide), which were higher than in the nontrastuzumab groups (1% [paclitaxel alone] and 8% [anthracycline and cyclophosphamide]) .…”

“…The incidence of New York Heart Association class III and IV cardiac dysfunction was also notably higher in patients who received trastuzumab with anthracycline and cyclophosphamide (16%) compared with those who received anthracycline and cyclophosphamide (3%), trastuzumab and paclitaxel (2%), or paclitaxel alone (1%) . Following the identification of trastuzumab‐associated cardiac events, subsequent trials of trastuzumab adopted stringent criteria for patient enrollment (excluding those at increased risk for cardiac adverse events), avoided concurrent use of trastuzumab with anthracyclines, implemented rigorous protocols for monitoring of cardiac function, and recommended discontinuation of trastuzumab upon detection of cardiac symptoms . In a retrospective analysis of women treated with HER2‐targeted therapy for metastatic breast cancer, most cases of symptomatic heart failure recovered with trastuzumab discontinuation and cardiac therapy .…”

“…Addressing CVD in patients with breast cancer is an important clinical issue. Because of their age and the long survival times associated with therapy, patients with breast cancer often display common risk factors associated with CVD, and the adverse cardiac effects of some breast cancer therapies, notably anthracyclines and trastuzumab, are widely documented . Although the cardiac effects of newer, targeted agents used to treat advanced breast cancer (e.g., endocrine therapies including CDK4/6 inhibitors) are substantially lower, routine, comprehensive cardiovascular assessment of all patients at baseline is widely recommended prior to initiating anticancer therapy, as well as during and after therapy, depending on the treatment and patient's risk of CVD.…”

Onco-metabolism: defining the prognostic significance of obesity and diabetes in women with brain metastases from breast cancer

“…Given that these findings could be confounded by obesity or diabetes-related comorbidities or toxicities, we assessed the incidence of pre-existing or development of peripheral neuropathy, chronic kidney disease (Stages III–V) [20], and cardiac morbidity, including acute coronary syndrome and left ventricular dysfunction [21] (Supplemental Data, Table 1). Overall, these toxicities and comorbidities were relatively uncommon.…”

Cardiac Toxicity of HER-2 Targeted Regimens

“…However, the few studies that have evaluated NT-proBNP use in trastuzumab have not found it to be a reliable predictor of subsequent CTRCD (Table 10.5). 58…”