Concomitant use of renin-angiotensin-aldosterone system inhibitors prevent trastuzumab-induced cardiotoxicity in HER2+ breast cancer patients: an institutional retrospective study

Background Cardiotoxicity is an adverse effect of trastuzumab (TRA) in the treatment of human epidermal growth factor 2 positive (HER2+) breast cancer. Current literature on the cardioprotective effects of agents targeted against the renin-angiotensin-aldosterone system (RAAS) and beta-blockers (BB) in TRA-treated HER2+ breast cancer patients is conflicting. We hypothesized that concurrent use of RAAS inhibitors would prevent TRA-induced cardiotoxicity (TIC).Methods and materials Surveillance ejection fraction (EF) at 3-month intervals up to 36 months obtained from echocardiogram or multigated acquisition (MUGA) scans were retrospectively compared to baseline EF in TRA-treated HER2+ breast cancer patients between 2011 to 2016 at a tertiary cancer center. TIC was defined as a decrease of EF by more than 15 EF percentage points from baseline on surveillance imaging. Cardiac medications and comorbidities were compared between patients with reduced EF secondary to TIC (rEF) and patients who did not experience TIC (pEF). A published clinical risk score (CRS) was applied to the patient population with calculated sensitivity analyses to determine if the CRS could predict TIC.Results Of 127 patients with TRA-treated HER2+ breast cancer, 11% developed cardiotoxicity resulting in discontinuation of TRA. Cardiotoxicity with reduced EF was seen as early as 3 months and at subsequent 3-month follow up intervals up to the 15-month follow-up. Co-existing arrhythmia, coronary artery disease (CAD), hypertension (HTN) and diabetes mellitus (DM) tended to infer an increased risk for cardiotoxicity. Patients with pEF were found to be concurrently on a RAAS inhibitor more than the rEF group (OR of 0.24, 95% CI 0.05-1.11, p 0.06). The CRS high-risk cut-off had a sensitivity of 0.17 (95% CI 0.03-0.49), specificity of 0.89 (95% CI 0.82-0.94), positive predictive value of 0.14 (95% CI 0.03-0.44) and negative predictive value of 0.91 (95% CI 0.84-0.95).Conclusion Our data suggest that the concurrent use of a RAAS inhibitors during TRA treatment may provide a protective effect against TIC and warrants further investigation. The low sensitivity and positive predictive value demonstrated that the CRS has minimal utility as a screening tool for prediction of patients at high risk for TIC. Therefore, closer surveillance of patients receiving TRA is warranted for early detection of TIC.