Cardioprotective effect of renin–angiotensin inhibitors and β-blockers in trastuzumab-related cardiotoxicity

Background: Trastuzumab-related cardiotoxicity (TRC) has been considered as reversible. However, recent studies have raised concern against reversibility of left ventricular (LV) systolic dysfunction in breast cancer patients treated with trastuzumab. In addition, the efficacy of medical treatment for heart failure (HF) including renin–angiotensin inhibitors and β-blockers has not been defined in TRC. Methods and results: We retrospectively studied 160 patients with breast cancer receiving trastuzumab in the adjuvant (n = 129) as well as metastatic (n = 31) settings in our institution from 2006 to 2015. During the median follow-up of 3.5 years, 20 patients (15.5%) receiving adjuvant trastuzumab and 7 patients (22.6%) with metastatic breast cancer developed TRC with a mean decrease in LV ejection fraction (EF) of 19.8%. By the multivariate analysis, lower LVEF before trastuzumab (OR 1.30; 95% CI 1.16–1.48; P = 0.0001) independently predicted subsequent development of TRC. LV systolic dysfunction was reversible in 20 patients (74.1%) with a median time to recovery of 7 months, which was independently associated with lower dose of anthracyclines (OR 1.03; 95% CI 1.01–1.07, P = 0.020) and an introduction of renin–angiotensin inhibitors and β-blockers (OR 19.0; 95% CI 1.00–592.2, P = 0.034). Conclusions: Irreversible decline in LVEF occurred in patients who underwent trastuzumab in combination with anthracyclines with a relatively high frequency. The lower cumulative dose of anthracyclines and HF treatment including renin–angiotensin inhibitors and β-blockers were both independent predictors to enhance LV functional reversibility in patients with TRC.