Survival in de novo versus metachronous metastatic breast cancer across molecular subtypes: A large real-world, propensity-matched analysis.

e12756 Background: Metastatic breast cancer (MBC) may present as de novo metastatic disease (dnMBC) or as metachronous recurrent metastatic disease (rMBC) following prior early-stage breast cancer. Differences in tumor biology and prior treatment exposure may contribute to survival differences. We compared survival outcomes between dnMBC and rMBC across major breast cancer subtypes using a large real-world database. Methods: We conducted a retrospective, real-world cohort study using the TriNetX research network. Adult female patients (≥18 years) with metastatic breast cancer were identified using structured diagnostic codes. Patients were classified as dnMBC if metastatic disease occurred within 3 months of initial diagnosis and as rMBC if metastatic disease occurred ≥13 weeks after diagnosis. Patients were stratified into four subtypes: HR+/HER2−, HR+/HER2+, HR−/HER2+, and triple-negative breast cancer (TNBC). The primary endpoint was overall survival (OS). Survival was assessed using Kaplan–Meier methods and log-rank tests. Propensity score matching (PSM) was performed within each subtype based on age, race/ethnicity, and major comorbidities. Results: After PSM, cohorts were well balanced. De novo metastatic presentation was consistently associated with superior OS across all subtypes (Table). Across subtypes, dnMBC demonstrated significantly lower mortality risk compared with rMBC, with higher long-term survival and unreached median OS in several groups. Conclusions: In this large real-world, propensity-matched analysis, dnMBC was consistently associated with superior OS compared with rMBC across all major breast cancer subtypes. Timing of metastatic presentation should be considered an important prognostic factor and stratification variable in metastatic breast cancer. Overall survival by breast cancer Subtype (dnMBC vs rMBC). Subtype HR (95% CI) p-value Survival % (dnMBC vs rMBC HR+/HER2- 0.55 (0.51-0.59) <0.0001 55.5 vs 33.1 HR+/HER2+ 0.60 (0.53–0.68) <0.0001 62.8 vs 40.9 HR-/HER2+ 0.62 (0.51–0.76) <0.01 58.8 vs 51.1 TNBC 0.63 (0.56–0.71) <0.0001 50.7 vs 36.4