Trastuzumab rezetecan significantly improved progression-free survival versus physician’s choice chemotherapy in HER2-low advanced breast cancer in the Phase 3 HORIZON-Breast06 trial, with the benefit holding in chemotherapy-naïve patients and the overall population. In a report based on ESMO Congress 2026 presentation (Abstract LBA13) and simultaneous publication in JAMA, the trial enrolled 551 patients who received no more than one prior chemotherapy line for advanced disease. For HR-positive patients, prior endocrine therapy was required. Key results showed a more than twofold improvement in median PFS among chemotherapy-naïve patients—16.6 months versus 6.8 months—with a hazard ratio of 0.25 (P<.001). Similar benefit appeared in the overall population, with median PFS of 16.4 months versus 6.8 months (HR 0.27; P<.001). Overall survival data were immature, and the report notes that head-to-head comparisons versus already approved ADCs are lacking, leaving competitive advantage over agents such as trastuzumab deruxtecan uncertain.