Safety of Permissive Cardiotoxicity of Trastuzumab in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

Cardiotoxicity is a recognized adverse effect associated with anti-HER2 therapies. The Trastuzumab-mediated cardiac dysfunction is not dose-dependent and lacks ultrastructural changes, allowing potential recovery after a few months. There is no consensus on the management of patients who develop cardiotoxicity. This meta-analysis aims to assess the safety of the permissive cardiotoxicity of Trastuzumab in patients with breast cancer. We searched PubMed, Cochrane Library, and Embase up to October 2023 for retrospective or prospective studies that investigated the safety of Trastuzumab in patients with breast cancer who continued Trastuzumab therapy after asymptomatic ejection fraction (EF) decline. We conducted a pooled meta-analysis for the subsequent cardiac events, cardiac mortality, and all-cause mortality. We assessed the quality of included studies using the Newcastle-Ottawa Scale and ROBIN-1 tool. A total of eight cohort studies (six retrospective and two prospective), comprising 222 patients, were found eligible and were included in our analysis. The pooled incidence of cardiac events, cardiac-related mortality, and all-cause mortality was 18% (95% CI 13% to 24%), 5% (95% CI 2% to 10%), and 8% (95% CI 2% to 28%), respectively. The incidence of symptomatic or severe cardiac events was lower in those who received cardioprotective medications concomitant with Trastuzumab. Most patients received either angiotensin-converting-enzyme inhibitors, beta-blockers, or a combination of both. Continuation of planned Trastuzumab therapy with concomitant use of cardioprotective medications can be a safe and effective approach for breast cancer control in patients with asymptomatic EF decline.