Beta-blockers, renin-angiotensin system inhibitors, and cardiovascular outcomes during trastuzumab therapy for HER2-positive breast cancer: a systematic review and meta-analysis of randomized controlled trials
Year: 2026
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: Background: Trastuzumab has substantially improved clinical outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, but treatment-related cardiac dysfunction may compromise treatment continuity and long-term cardiovascular health. This systematic review and meta-analysis evaluated whether prophylactic beta-blockers or renin-angiotensin system inhibitors (RASIs) preserve left ventricular ejection fraction (LVEF) and reduce cardiotoxicity during trastuzumab-based therapy.Methods: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception through March 31, 2026. Randomized controlled trials enrolling adults with HER2-positive breast cancer receiving trastuzumab-based therapy were eligible. LVEF change was pooled as a mean difference (MD) in percentage points, and cardiotoxicity incidence was pooled as a risk ratio (RR), both with 95% confidence intervals (CIs). Prespecified subgroup analyses were conducted by drug class, with formal interaction testing.Results: Five randomized controlled trials involving 848 patients were included. Four trials involving 358 participants contributed to the LVEF analysis. Overall, prophylactic cardioprotective therapy was not significantly associated with greater LVEF preservation (MD, 1.93 percentage points; 95% CI: −0.07 to 3.93; I2=67.4%), and the 95% prediction interval ranged from −4.34 to 8.19 percentage points. Within the drug-class subgroups, RASIs were associated with greater LVEF preservation (MD, 2.90 percentage points; 95% CI: 0.92 to 4.87), whereas the estimate for beta-blockers was not statistically significant (MD, 1.47 percentage points; 95% CI: −1.35 to 4.29). However, the interaction test showed no significant difference between drug classes (P for interaction =0.416). Five trials involving 821 participants reported cardiotoxicity incidence. Cardioprotective therapy did not significantly reduce cardiotoxicity overall (RR, 0.97; 95% CI: 0.66 to 1.41; I2=31.4%). Neither RASIs (RR, 0.97; 95% CI: 0.60 to 1.57) nor beta-blockers (RR, 0.97; 95% CI: 0.32 to 2.91) significantly reduced cardiotoxicity incidence, and the interaction test showed no significant difference between drug classes (P for interaction =0.995).Conclusions: Current randomized evidence does not demonstrate a clear overall benefit of prophylactic beta-blockers or RASIs for preserving LVEF or preventing cardiotoxicity during trastuzumab-based therapy. Although RASIs showed a significant within-class association with LVEF preservation, the nonsignificant interaction test precludes conclusions regarding class superiority. Larger randomized trials with standardized cardiac outcomes and risk-stratified designs are required.
Source: Translational Cancer Research
Institution: University of Health and Rehabilitation Sciences
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7224122417