Primary cardioprotective effect of sacubitril/valsartan in breast cancer patients receiving adjuvant therapy

Aims Cancer therapy‐related cardiac dysfunction (CTRCD) can adversely affect clinical outcomes in patients with cancer. The cardioprotective effects of sacubitril/valsartan in preventing CTRCD remain underexplored. This study aimed to evaluate the cardioprotective effects of sacubitril/valsartan in preventing CTRCD in patients with early breast cancer during the first year after adjuvant therapy. Methods and results One hundred newly diagnosed treatment‐naïve patients with early breast cancer (50.4 8.5 years, 98% women) were enrolled prospectively between May 2021 and July 2023. Participants were randomized at a 1:4 ratio to receive sacubitril/valsartan, starting 3 days before cancer therapy at an initial dose of 12.25/12.75 mg twice daily, titrated to a maximum dose of 24.5/25.5 mg twice daily ( n = 20), or standard care with monitoring and initiation of standard therapies upon CTRCD occurrence ( n = 80) for 12 months. There were no significant differences in the baseline demographic characteristics between the two groups. The mean doxorubicin‐equivalent dose was 276.0 ± 48.5 mg/m 2 in the sacubitril/valsartan group and 269.5 ± 57.9 mg/m 2 in the standard care group ( p = 0.175). The primary endpoint was the development of CTRCD, defined as a relative ≥15% decline in global longitudinal strain (GLS) or a reduction in left ventricular ejection fraction by ≥10 percentage points to below 50%. Of the 100 randomized patients, 95 (95%) completed the trial. No patient in the sacubitril/valsartan group developed CTRCD, whereas 21 patients (26.3%) in the standard care group did ( p = 0.006). All events of CTRCD were identified based on significant decline in GLS. Conclusions Low‐dose sacubitril/valsartan may prevent CTRCD in treatment‐naïve patients with early breast cancer undergoing adjuvant therapy within the first year. Large phase III clinical trials are needed to confirm these findings.