Trastuzumab rezetecan (SHR-A1811) delivered a substantial progression-free survival improvement in HER2-low advanced breast cancer in the phase 3 HORIZON-Breast06 trial, beating physician’s-choice chemotherapy. In chemotherapy-naïve patients, median PFS more than doubled to 16.6 months versus 6.8 months with chemotherapy (HR 0.25; 95% CI 0.19–0.33; P<.001). The benefit was also seen in the overall population (median PFS 16.4 vs 6.8 months; HR 0.27; 95% CI 0.21–0.34; P<.001). The trial, presented by Ying Fan, MD (Chinese Academy of Medical Sciences and Peking Union Medical College) at ESMO Congress 2026 (Abstract LBA13) and published in JAMA, enrolled 551 patients with HER2-low disease. Patients received no more than one prior line for advanced disease, with hormone receptor-positive patients also requiring prior endocrine therapy. Overall survival data were immature, but subgroup analyses favored the ADC across prespecified categories, with the company highlighting consistency regardless of HR status. Head-to-head comparisons versus existing ADCs were not available at the time of reporting.