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Simple Summary: Despite advances in treatment generated by clinical trials in metastatic breast cancer (MBC), their impact on routine daily practice and the reflection of the outcome within the community remains unclear. This study evaluates time-related differences in treatment patterns and outcome in a real-world patient population with MBC over a ten-year timeframe. Except for the HER2+ subgroup, which showed a significant survival benefit with the incorporation of novel agents, we failed to identify significant variations in outcomes for the remaining subgroups. A consistent feature we observed was the challenge in treating TNBC, which had the worst prognosis in both time-related cohorts. Elucidation of biologic characteristics to identify novel treatment options remains an unmet need to improve outcomes in TNBC. The favorable survival attained with routine endocrine agents in the luminal A subgroup suggests that barriers in access to CDK inhibitors may not have a negative impact on the outcome in subgroups of hormone receptor-positive patients, constituting an appealing strategy for communities with limited resources. This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% (n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0–55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options. [ABSTRACT FROM AUTHOR]