Abstract
Background: Trastuzumab is associated with the risk of cardiotoxicity. Here, we aim to explore interventions for preventing trastuzumab-related cardiotoxic effects in breast cancer patients.Methods: A systematic review was performed including trials of breast cancer patients with intervention to prevent cardiotoxicity of trastuzumab. Trials were searched through databases including PubMed, Embase, and Cochrane Library.Results: Eight RCTs were included. Five trials reported the outcomes of short-duration interventions, including 6-month and 9-week durations, and only 9-week treatment has a significant difference from the 12-month group (OR 0.38; 95% CI 0.18–0.83) using cardiotoxicity as the outcome. However, 6-month treatment turned out to yield less occurrence of trastuzumab discontinuation (OR 0.32; 95% CI 0.24–0.42). Three trials reported interventions of cardioprotective drugs, and there is no significant difference shown in any cardioprotective group compared with placebo (cardiotoxicity outcome: angiotensin-converting enzyme inhibitor: OR 0.48; 95% CI 0.057–2.3; angiotensin receptor blocker: OR 1.3; 95% CI 0.12–14; β-blocker: OR 0.48; 95% CI 0.057–2.3; trastuzumab interruption outcome: angiotensin-converting enzyme inhibitor: OR 0.45; 95% CI 0.12–1.3; angiotensin receptor blocker: OR 0.87; 95% CI 0.15–4.8; β-blocker: OR 0.41; 95% CI 0.11–1.2).Conclusion: Only the 9-week group has a significant difference from the 12-month group using cardiotoxicity as the outcome. And 6-month treatment turned out to yield less occurrence of trastuzumab discontinuation. The use of cardioprotective drugs failed to prevent trastuzumab-related cardiotoxic effects in breast cancer patients.
Highlights
Female breast cancer has leapt to be the most commonly diagnosed cancer surpassing lung cancer, with an estimated 2.3 million new cases in 2020 (Sung et al, 2021)
A total of 1,691 citations were identified through electronic searches, and eight randomized controlled trials (RCTs) were selected for our study (Figure 1) (Mavroudis et al, 2015; Boekhout et al, 2016; Pituskin et al, 2017; Conte et al, 2018; Joensuu et al, 2018; Earl et al, 2019; Guglin et al, 2019; Pivot et al, 2019)
Five studies assessed whether fewer cardiac events can be achieved with reduced treatment duration, including a 6-month vs a 12month schedule (Mavroudis et al, 2015; Earl et al, 2019; Pivot et al, 2019) and a 9-week vs a 12-month schedule (Conte et al, FIGURE 3 | Forest plots of the effect of interventions for reducing cardiotoxicity in breast cancer patients receiving trastuzumab. (A) Short duration of trastuzumab using cardiotoxicity as the outcome; (B) cardioprotective drug intervention using cardiotoxicity as the outcome; (C) cardioprotective drug intervention using interruptions in trastuzumab therapy as the outcome. 2018; Joensuu et al, 2018)
Summary
Female breast cancer has leapt to be the most commonly diagnosed cancer surpassing lung cancer, with an estimated 2.3 million new cases in 2020 (Sung et al, 2021). Previous meta-analysis has shown that shorter treatment durations decreased the risk of severe cardiac toxicity compared to 12 months of trastuzumab (Eiger et al, 2020). Recent studies demonstrated that cardioprotective drugs might be likely to reduce the cardiotoxicity effect caused by the 12-month duration of trastuzumab in breast cancer patients (Guglin et al, 2019). Whether these drugs can confer cardioprotective effects in trastuzumab-treated patients is still unclear. We aim to explore interventions for preventing trastuzumab-related cardiotoxic effects in breast cancer patients.
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