TRASTUZUMAB ASSOCIATED LEFT VENTRICULAR DYSFUNCTION: CAN THE NEED FOR TREATMENT INTERRUPTION BE PREDICTED AND DOES INTERRUPTION AFFECT CARDIOVASCULAR OR ONCOLOGIC OUTCOMES?

Abstract

Trastuzumab (T) has been shown to significantly reduce the risk of breast cancer recurrence. Current standards of practice recommend administering adjuvant T in 17 doses over one year. However, the use of T may be associated with an often reversible, left ventricular dysfunction (LVD). When LVD occurs, clinicians must decide whether to interrupt or continue treatment. This retrospective study was conducted to assess the cardiovascular and oncologic outcomes associated with each of these clinical decisions in the context of mild LVD. We included patients who received adjuvant T therapy in British Columbia for local breast cancer between September 2005 and December 2013 and experienced a treatment-emergent drop in left ventricular ejection fraction (LVEF) to 40-49%. The study cohort was divided into two groups based on whether or not T was held at any point during the course of therapy. Charts were reviewed for demographic information, cardiovascular events, and cancer outcomes. 2401 patients received adjuvant T during the study period. Of these, 261 (10.9%) patients had a LVEF decline to 40-49%. T was interrupted in 229 (87.7%), while 32 (12.3%) underwent continuous therapy. Pre-existing structural heart disease and cardiac risk factors, including smoking, hypertension, and diabetes, were not significantly more prevalent in the interruption group. Adverse cardiovascular outcomes (subsequent LVEF drop to < 40% or clinical heart failure) were more frequent in those who had treatment interruption compared to those who received continuous T. The number of patients experiencing a cancer relapse in the T interruption and continuous groups were 38 (16.6%) and 2 (6.25%), respectively (P=0.19). Among those receiving 17 doses of T with a temporary interruption in therapy, there was a 17.5% breast cancer recurrence rate. Pre-existing cardiovascular disease and cardiac risk factors did not appear to increase the likelihood of a T hold. Following the development of mild LVD, the risks of adverse cardiovascular outcomes were not increased by continuation of T. However, holding T was associated with a 10% absolute risk increase in breast cancer recurrence. Moreover, even when 17 doses of T were given, there was an 11% absolute risk increase in breast cancer relapse when trastuzumab was transiently held. While there results are not statistically significant, they suggest the need for a larger study to inform evidence-based guidelines on the interruption of T in the context of LVD.