Cardiotoxicity of newer HER2-Directed therapies in breast cancer: A systematic review and meta-analysis of incidence and comparative risk
In brief
New HER2-targeted agents cause heart toxicity in ~5% of patients, similar to trastuzumab
A meta-analysis of 58 studies (35,984 breast-cancer patients) found that about 5% experienced a drop in left-ventricular ejection fraction with newer HER2-directed drugs, and overall serious cardiac events were rare. The risk was not higher than with standard trastuzumab regimens, though more frequent cardiac monitoring identified more cases, highlighting the need for uniform surveillance standards.
- Journal
- Breast (Edinburgh, Scotland) (Q1)
- Published
- 20 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Senthamizhan Sundaramoorthy, Narendhar Gokulanathan, Rona Joseph P, Anoop Tm, Sherin P Mathew, Harpreet Kaur, et al.
- PMID
- 42520572
- DOI
- 10.1016/j.breast.2026.104880
Why clinicians should know about it
- Picked for Public Health, Environmental and Occupational Health (top studies of the week, 2 August 2026).
Abstract
PURPOSE: This systematic review and meta-analysis aimed to estimate the incidence and comparative risk of cardiotoxicity associated with newer HER2-targeted therapies compared with conventional trastuzumab-based regimens. It also evaluates the differences across drug classes, clinical subgroups, and monitoring strategies. MATERIALS AND METHODS: PubMed, Embase, CENTRAL, and Scopus were searched (2005-2025) for randomized controlled trials (RCTs) and prospective studies reporting cardiac outcomes with HER2-directed therapies. Pooled cardiotoxicity incidence was calculated from single-arm studies and intervention arms of RCTs and risk ratios (RRs) from RCTs using random-effects models. Subgroup analyses were performed by drug class, anthracycline exposure, HER2 category, age, and cardiac monitoring frequency. Certainty of evidence was assessed using GRADE. RESULTS: Fifty-eight studies (35,984 patients) were included. Pooled cardiotoxicity incidence was 5.08% (95% CI, 3.37 to 7.58) with left ventricular ejection fraction (LVEF) decline in 4.68% patients, and other cardiac events were each reported in <1% patients. Across 32 RCTs, no significant difference in cardiotoxicity was observed between newer HER2-directed therapies and trastuzumab-based comparator regimens (including trastuzumab monotherapy or trastuzumab combined with chemotherapy, with or without pertuzumab) (RR, 0.97; 95% CI, 0.73 to 1.29). Subgroup analyses showed variability across study characteristics, with higher incidence observed in studies using more frequent cardiac monitoring (8.15%; 95% CI, 3.13 to 19.61%, P > 0.05). CONCLUSION: Newer HER2-directed therapies demonstrate low cardiotoxicity, with rare serious events and no evidence of excess risk compared with conventional trastuzumab-based regimens. These findings support cardiac safety but suggest the need for standardized monitoring and uniform cardiotoxicity definitions.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.