Background: Lower baseline radiological tumor burden is associated with more favorable outcomes for patients with metastatic non-small cell lung cancer and melanoma treated with immunotherapy. However, minimal data is available for metastatic breast cancer patients. This is despite immunotherapy, in combination with chemotherapy, now being standard-of-care for a subset of metastatic breast cancer patients who have triple-negative disease and are PD-L1 positive. Methods: We reviewed data of 82 patients with metastatic breast cancer consecutively treated at our institution from August 2015 to October 2021, who received > 1 dose of an immune checkpoint inhibitor (anti-PD-1 or -PD-L1) within the context of a clinical trial. Baseline tumour burden was assessed by a single radiologist and calculated as sum of Response Evaluation Criteria in Solid Tumours 1.1 baseline target lesions (baseline tumour size [BTS]) or as sum of all measurable baseline lesions (total tumour burden [TTB]); the impact of both parameters on treatment outcomes was investigated. Treatment outcomes assessed were clinical benefit rate (complete response, partial response or stable disease for 6 months or more [CBR6]), disease free survival (DFS) and overall survival (OS). Multivariate analysis adjusted for ECOG status, line of treatment (first line vs second line or beyond), and whether immunotherapy was given in combination with chemotherapy or as monotherapy. Results: A total of 82 patients were included in the analysis. 43 patients (52%) received combination chemotherapy with immunotherapy, 39 patients (48%) received immune checkpoint inhibitor monotherapy. Median BTS and TTB were 36.5mm (range 0 -204mm) and 43mm (range 0 – 1123mm) respectively. CBR6 was significantly associated with BTS (p=0.004) and TTB (P=0.002) quartiles, with clinical benefit time progressively increasing with decreasing tumor burden quartiles. Both increasing BTS (p<0.001) and TTB (p<0.001) across quartiles were significantly associated with shorter OS. There was a numerical, but not statistically significant, association between both parameters as quartiles (BTS, p=0.25; TTB, p=0.07) and PFS. In the bottom BTS quartile, 32% of patients were progression-free and 95% alive at 12 months, compared with 15% and 40% respectively in the top quartile. Similar results were seen when TTB was used as the baseline measurement: 32% progression-free and 95% alive at 12 months in the bottom quartile compared with 1% and 33% in the top quartile. Multivariate analysis confirmed that both BTS and TTB, considered as continuous variables, are independently associated with OS. Conclusions: Lower baseline radiological tumor burden is associated with better outcomes in patients with metastatic breast cancer treated with immune checkpoint inhibitors.