Trastuzumab–deruxtecan (T-DXd), an innovative antibody-drug conjugate, has markedly boosted survival rates and clinical outcomes for individuals with advanced HER2-positive/HER2-low breast cancer, as evidenced by randomized controlled trials, alongside a tolerable toxicity profile. Findings from these trials provide essential insights for routine patient care, including populations often ineligible for trial participation due to strict entry criteria. Through this narrative review, we summarize and critically appraise published real-world investigations on T-DXd therapy in metastatic breast cancer (MBC) patients expressing HER2-positive or HER2-low status, focusing on clinically relevant scenarios. A PubMed query revealed nine published real-world analyses of T-DXd. These retrospective cohorts involved a combined total of 7146 patients. Furthermore, 5/9 investigations encompassed HER2-low MBC cases. Patients typically exhibited extensive tumor involvement, commonly affecting lungs and liver. Key topics explored include individuals with multiple prior treatments, reduced performance status, comparisons between HER2-positive and HER2-low subtypes, central nervous system metastases, geriatric populations, interstitial lung disease risks, general tolerability, and treatment dose adaptations. This evaluation validates the therapeutic effectiveness of T-DXd reported in everyday practice settings and highlights an advantageous tolerability profile with adverse events that can be effectively managed.
