Cancer Therapy–Induced Cardiac Toxicity in Early Breast Cancer

landscape of early breast cancer has changed dramat- ically with significant advancements in early screening and diagnosis and curative-intent therapies. Indeed, breast cancer-specific survival has improved by 20% during the past 30 years, and 5-year survival is now 98% for early-stage disease. In women with early breast cancer, particularly those 65 years of age, cardiovascular disease (CVD) is now the predominant cause of mortality as indicated by Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data. 2 Additionally, these women are also at increased risk of CVD compared with age-matched women without a history of breast cancer. ignificant cardiac safety concerns about anticancer therapy were first described by Von Hoff and colleagues, 4 identifying dose-dependent and progressive left ventricular (LV) dysfunction manifesting as symptomatic heart failure in patients receiving anthracyclines. From this work and others, More recently, randomized trials have demonstrated that human epidermal growth factor receptor 2 (HER2)-directed monoclonal antibodies (ie, trastuzumab) and newer multitargeted small-molecule inhibitors interfere with molecular pathways crucial to normal cardiac homeostasis, 9 resulting in relatively high incidences of subclinical and overt cardiac toxicity. Although cardiac toxicity with newer therapies has demonstrated reversibility, 11 recovery of LV function after treatment cessation is uncertain at this time. 12 Thus, to identify those individuals at high risk of cardiac toxicity, baseline measurement of LV ejection fraction (LVEF) is recommended by the American College of Cardiology (ACC) and American Heart Association (AHA) as standard of care for all breast cancer patients being considered for potentially cardiac-toxic treatment regimens. In addition, measurement of LVEF is Food and Drug Administration (FDA) mandated in all registrational breast cancer adjuvant trials involving an anthracycline-or a trastuzumab-containing regimen. Finally, use of endocrine therapy (eg, tamoxifen and aromatase inhibitors) in women with hormone receptor-positive breast cancer may also increase the risk of cardiovascular complications. espite the rapidly changing landscape of breast cancer management and the resultant changes in cardiovascular safety, several critical issues in the emerging field of "cardiooncology" remain unresolved. To ensure that this field keeps pace, a full understanding of the incidence, magnitude, and consequences of cardiovascular side effects of adjuvant therapy is an essential first step in optimizing early breast cancer management. Against this background, the purpose of this article is to comprehensively review several pivotal unaddressed issues concerning the definition, incidence, detection, and clinical importance of cardiac toxicity in early breast cancer. The evidence supporting the efficacy of preventive and treatment strategies is also discussed.