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.
4 affiliations
- 1Department of Breast Surgery, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, China.
- 2Department of Oncology & Radiotherapy, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, China.
- 3Department of Pathology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, China.
- 4Department of Gynecological Neoplasms, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, China.
Abstract
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. 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. 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). 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.
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BibTeX
@article{liu2026betablockers,
title = {{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.}},
author = {Yukun Liu and Linlin Zhang and Jie Guan and Zhimei Wang and Xiaodong Luan},
journal = {Translational cancer research},
year = {2026},
month = sep,
doi = {10.21037/tcr-2026-1107},
url = {https://europepmc.org/article/MED/42997685},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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.
AU - Yukun Liu
AU - Linlin Zhang
AU - Jie Guan
AU - Zhimei Wang
AU - Xiaodong Luan
PY - 2026
DA - 2026/09/29
JO - Translational cancer research
DO - 10.21037/tcr-2026-1107
UR - https://europepmc.org/article/MED/42997685
AB - 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. 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. 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). 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.
SN - 2218-676X
SN - 2219-6803
ER -