Prevention of cardiotoxicity in breast cancer patients: A randomized prospective study

Abstract

Background: Adjuvant anthracyclin chemotherapy (ANTC) and trastusumab are documented to prolong survival in breast cancer patients. However, these drugs are well known to induce Left Ventricular Systolic Dysfunction (LVSD). Multiple studies showed that acetyl choline-esterase inhibitor (ACEIs) and beta Blockers (BBs) can prevent LVSD. Methods: One hundred and twenty six patients with M0 breast cancer patients to be treated with ANTC±trastuzumab were randomized to an intervention group (group 1) (n=63 patients) which received cardioprotective drugs; (ACEI;enalapril) and (BB;carvedilol) or to a control group which did not receive cardioprotective drugs (group 2) (n=63 patients). To evaluate systolic and diastolic functions conventional echocardiography (Simpson method and M- mode) and cardiac magnetic resonance imaging (CMR) were performed at baseline, after 3 cycles and 6 cycles of ANCT, and after 1 year of follow-up. Cardioprotective drugs received: Both enalapril and carvedilol were started at least 24 hours before the first chemotherapy cycle. Results: In the intervention group 58 patients had 3 cycles ANTC, 6 patients received 6 cycles ANTC, and 12 patients received trastuzumab. Whereas in the control group 47 patients had 3 cycles ANTC, 16 patients were given 6 cycles ANTC and 18 patients received trastusumab. After 3 ANTC cycles, LVEF did not change in group 1 (64.35%at baseline vs. 63.59%, p 0.2) but decreased by M- mode in the control group (64.84% at baseline vs. 63.42%, p 0.03) associated with statistically significant deterioration of diastolic function grades. At 1 year follow-up, while no change was observed in LVEF in group 1, there was decrease in LVEF by CMR in group 2 (65.78% at baseline, 61.48% at 1 year, p 0.048). No cases were detected with heart failure or with final EF<45% in either group. Compared to controls, the intervention group had a statistically significant lower incidence of decrease EF≥10% after finishing ANTC by CMR(1.9% vs. 12.5%, p 0.04). Conclusions: Combined prophylaxis with ACEI (enalapril) and BB (carvedilol) may prevent LVSD in patients with non-metastatic breast cancer treated with anthracyclines containing chemotherapy±trastuzumab. The clinical relevance of this strategy should be confirmed in larger randomized studies.