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Background: Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008. Patients and methods: We evaluated overall survival (OS) in the whole cohort (N ¼ 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HRþ/HER2À; N ¼ 13 590), HER2þ (N ¼ 3919), and triple-negative breast cancer (TNBC; N ¼ 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD). Results: The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P ¼ 0.009, using 2008 as reference]. This effect is driven by the HER2þ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P ¼ 0.41, using 2008 as reference] nor among those with HRþ/HER2e MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P ¼ 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HRþ/HER2e and TNBC cohorts, respectively, whatever YOD. Conclusion: OS has dramatically improved among HER2þ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed.