Cancer therapy-induced cardiac toxicity in early breast cancer: addressing the unresolved issues.

Abstract

The landscape of early breast cancer has changed dramatically 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.1 As a consequence, the risk and nature of adjuvant therapy–induced immediate and late-occurring cardiovascular injury have similarly evolved. 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.3 Significant 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,5,6 anthracycline-induced cardiac toxicity7,8 is now a well-recognized adverse side effect. 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.10 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.13,14 In addition, measurement …