Safety of withdrawal of pharmacological treatment after recovery from HER2 therapy-related cardiac dysfunction: the HER-SAFE trial
In brief
Stopping heart-failure meds after HER2 recovery yields 2% silent decline
In the HER-SAFE trial of 90 breast-cancer survivors whose heart function had normalized after anti-HER2 therapy, withdrawing heart-failure drugs caused a modest asymptomatic drop in cardiac strain in 1 patient (2%); no one developed symptoms, hospitalisations, or death over 12 months. The finding suggests routine continuation may be unnecessary, but larger studies are needed to confirm safety.
- Journal
- European heart journal (Q1)
- Published
- 30 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- B Dowsing, H-M Dehbi, M S Andres, R Chung, A Oashou, J M Wilson, et al.
- PMID
- 42669033
- DOI
- 10.1093/eurheartj/ehag707
Why clinicians should know about it
- Picked for Biochemistry (medical) (top studies of the week, 6 September 2026): Not relevant to metabolic biochemistry
Abstract
BACKGROUND: Heart failure therapy (HFT) is routinely continued in breast cancer survivors after recovery from anti-HER2 cancer therapy-related cardiac dysfunction (CTRCD), despite limited evidence. HER-SAFE is the first randomised trial to assess HFT withdrawal in this population. METHODS: In this open-label, multicentre, randomised controlled trial, breast cancer survivors with recovered anti-HER2 CTRCD (asymptomatic, left ventricular ejection fraction [LVEF] ≥50%, normalised biomarkers) were randomised to HFT withdrawal or continuation. Antecedent CTRCD was mild (relative global longitudinal strain [GLS] decline >15%, LVEF ≥50%), moderate (LVEF fall >10% to <50%), or severe (LVEF <40%). The primary endpoint was a moderate or severe CTRCD event over 12 months analysed by intention to treat; secondary endpoints included serial cardiac function, biomarkers, and quality of life. RESULTS: Between July 2023 and June 2025, 90 patients were randomised (all female; median age 50 years [IQR 43-59]; median 17.3 months [IQR 7.7-33.2] since CTRCD recovery; HFT predominantly renin-angiotensin system inhibitors [98%] and beta-blockers [88%]) - 46 randomised to HFT withdrawal (1 lost to follow-up) and 44 to continuation. The primary endpoint occurred in 1 of 45 with withdrawal (moderate asymptomatic CTRCD) versus 0 of 44 with continuation (between-group difference 2.2pp; 90% CI upper limit 9.4pp). No cardiovascular deaths, heart failure hospitalisations or symptomatic CTRCD occurred. Cardiac magnetic resonance-derived LVEF remained stable in both arms at 12 months (between-group difference -0.8% [-2.0 to +0.4], p=0.21). CONCLUSIONS: Among breast cancer survivors with recovered anti-HER2 CTRCD, HFT withdrawal was not associated with symptomatic events or significant between-group difference in LVEF at 12-months.
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.