Safety of withdrawal of pharmacological treatment after recovery from HER2 therapy-related cardiac dysfunction: the HER-SAFE trial
Key result
Withdrawing heart failure therapy in recovered anti-HER2 dysfunction yields a ~2% CTRCD rate versus continuation.
- between-group difference +2.2pp
- 90% CI upper limit 9.4pp
- n=90
Why the study?
Heart failure therapy is routinely continued in breast cancer survivors after recovery from anti-HER2 cancer therapy-related cardiac dysfunction, despite limited evidence.
Does heart failure therapy withdrawal safely maintain cardiac function without increasing moderate or severe CTRCD events in breast cancer survivors with recovered anti-HER2 CTRCD?
Key Points
- To determine whether heart failure therapy can be safely withdrawn in breast cancer survivors who have recovered from anti-HER2 cancer therapy-related cardiac dysfunction.
- Open-label, multicentre, randomized controlled trial allocating 90 breast cancer survivors with recovered anti-HER2 cardiac dysfunction (LVEF ≥50%, normalized biomarkers) to heart failure therapy withdrawal (n=46) or continuation (n=44).
- Assessed the primary endpoint of moderate or severe cardiac dysfunction relapse over 12 months by intention to treat, along with serial cardiac magnetic resonance and biomarker evaluations.
- Moderate asymptomatic cardiac dysfunction occurred in 1 of 45 patients in the withdrawal arm versus 0 of 44 patients in the continuation arm (between-group difference 2.2 percentage points; 90% CI upper limit 9.4 percentage points).
- Zero cardiovascular deaths, heart failure hospitalizations, or symptomatic cardiac dysfunction events occurred in either study arm over 12 months.
- Cardiac magnetic resonance-derived LVEF remained stable in both arms at 12 months (between-group difference -0.8% [95% CI -2.0% to +0.4%], p=0.21).
Study Design
Type
RCT (n=90)
Blinding
Open-label
Randomization
Randomised
Multicenter
Yes
Structured PICO
Does heart failure therapy withdrawal safely maintain cardiac function without increasing moderate or severe CTRCD events in breast cancer survivors with recovered anti-HER2 CTRCD?
P
Population
90 female breast cancer survivors with recovered anti-HER2 cancer therapy-related cardiac dysfunction, followed for 12 months.
I
Intervention
Heart failure therapy (HFT) withdrawal
C
Comparator
Heart failure therapy (HFT) continuation
O
Outcome
Moderate or severe CTRCD event over 12 monthssafety
Main Result
Effect estimate: between-group difference 2.2pp (95% CI 90% CI upper limit 9.4pp)
Absolute Event Rate: 2.2% vs 0%
Withdrawal of heart failure therapy in breast cancer survivors with recovered anti-HER2 cardiac dysfunction appears safe, with no significant increase in symptomatic events or LVEF decline at 12 months.
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Our study provides the first evidence that heart failure therapies can be safely stopped in survivors whose hearts have recovered, with the support of ongoing close monitoring. We hope these findings will be encouraging for survivors and their doctors, giving hope for a future free from treatment.”
“Delighted to have presented HER-SAFE as a late breaking clinical trial at ESC 2026. A first in population randomised controlled trial of heart failure therapy withdrawal in breast cancer survivors with recovered anti-HER2 cardiotoxicity. HFT withdrawal appears feasible in most, with stable CMR derived cardiac function over 12 months.”
“hugely encouraging”
Implication
Supports de-escalation of heart failure therapy after anti-HER2 CTRCD recovery; first RCT challenges routine indefinite continuation.
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.
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Cite This Study
Dowsing et al. (2026) conducted an RCT in Recovered anti-HER2 cancer therapy-related cardiac dysfunction (n=90). Heart failure therapy withdrawal vs. Heart failure therapy continuation was evaluated on Moderate or severe CTRCD event over 12 months (between-group difference 2.2pp, 95% CI 90% CI upper limit 9.4pp). Heart failure therapy withdrawal in breast cancer survivors with recovered anti-HER2 cardiac dysfunction resulted in 1 of 45 moderate or severe CTRCD events versus 0 of 44 with continuation.