Primary Cardioprotective Effect of Sacubitril/Valsartan in Breast Cancer Patients Receiving Adjuvant Therapy

Abstract 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/m2 in the sacubitril/valsartan group and 269.5 ± 57.9 mg/m2 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.