Background: Trastuzumab deruxtecan (TDXd), an antibody drug conjugate, was first approved in the UK for the treatment of human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) in 2021. We aimed to review the efficacy and tolerability of TDXd in a real-world UK setting. Methods: We collected clinical and demographic data from medical records on HER2+ mBC patients treated with TDXd in the UK from Jan 2021 to Dec 2023 inclusive. This included: radiological response, the frequency of dose reductions and treatment delays, and reasons for discontinuation. Clinical trial patients were excluded. Descriptive statistical techniques were applied. Results: Data was collected from 26 UK cancer centres on 280 patients. The median age at TDXd initiation was 56 years (range 29-85). Median treatment duration was 9 cycles (range 1-40). 239 patients (85%) had visceral disease. 257 and 196 patients (92% and 70%, respectively) had received prior Trastuzumab and Pertuzumab, respectively. 233 patients (83%) had received prior TDM1. The median number of lines of treatment prior to TDXd was 3 (range 1 to 9). 20 patients (7%) were initiated on a reduced dose and 115 further patients (41%) required at least one dose reduction. 151 patients (54%) had at least one dose interruption due to: infection or neutropenia (n=61), other toxicity (n=85), interstitial lung disease (ILD) investigation (n=39), patient request (n=81), other concurrent illness (n=10), and cardiac investigation (n=6). Of these, 55 patients had more than one treatment break. 157 patients (56%) had discontinued TDXd treatment due to: disease progression or death (n=100), drug toxicity (n=39) of which 22 were due to ILD, and patient choice (n=8). 123 patients remained treatment at the time of analysis. The overall response rate of TDXd was 63% overall: stable disease 23%, partial response 56%, complete response 7%. Conclusions: The real-world data set is not directly comparable to either the DB02 or DB03 trials, as it included patients who had received TDXd in both the second line and later line settings. However, the majority (80%) of these patients were treated in the third line and beyond. The rates of drug interruption and reduction were higher in the real-world data set than in DB02, which may impact on efficacy in the real-world setting. Overall response rate is similar between trial data and our real-world data, although the latter was not measured by RECIST. Data collection is ongoing, including an analysis of real-world progression free survival.