Cardiac Surveillance Guidelines for Trastuzumab-Containing Therapy in Early-Stage Breast Cancer: Getting to the Heart of the Matter

Trastuzumab-containing regimens for breast cancer have significantly improved survival both in the early-stage and metastatic settings.1-8 Nevertheless, given the early signals of cardiotoxicity, a prevailing concern exists regarding the risk of cardiotoxicity, defined as a decline in left ventricular ejection fraction (LVEF) both asymptomatic and symptomatic. This concern that LVEF decline would be an early and actionable surrogate for subsequent development of congestive heart failure (CHF) led to the design and implementation of specific eligibility criteria and LVEF surveillance guidelines for the pivotal randomized adjuvant trials. These guidelines were subsequently adopted as the standard of care. However, it is increasingly unclear whether these specific recommendations are justified for all patients. Resolution of this matter is critical for our community because adherence to these guidelines was recently proposed as a quality metric.9 This issue raises the general question of the level of evidence needed to accept a toxicity screening schedule as a quality indicator. If following these guidelines is not associated with improved outcomes, then adherence to them as a quality metric should be challenged. Cardiotoxicity screening can serve to illuminate this issue. Here, we review the historical events that led to the development of the current guidelines and highlight critical knowledge gaps with regard to the benefits of screening and intervention.