Temporal Trends in Clinicopathological Features and Outcomes of De Novo Metastatic Luminal A Breast Cancer: A Retrospective Multicenter Analysis (2017–2025)

Whether clinicopathological features of de novo Luminal A metastatic breast cancer (MBC) have evolved across recent diagnostic periods remains unclear. In this retrospective, multicenter cohort study, we evaluated temporal changes in tumor biology and outcomes among 401 women diagnosed with de novo Luminal A MBC (ER/PR-positive, HER2-negative, Ki-67 ≤ 14%) between 2017 and 2025. Patients were stratified into four consecutive diagnostic periods spanning pre-pandemic, pandemic, and post-pandemic phases. A progressive increase in tumor proliferative activity was observed, with mean Ki-67 rising from 6.38% to 13.48% (<i>p</i> < 0.001), accompanied by declining ER/PR expression and increasing tumor size and histologic grade. Receiver operating characteristic analysis identified 9.5% as the optimal Ki-67 cutoff for overall survival (AUC = 0.785; <i>p</i> < 0.001). Both Ki-67 ≥ 9.5% and later diagnostic period independently predicted poorer survival in multivariable models (HR: 2.106 and 2.412; both <i>p</i> < 0.001). These findings suggest a temporal shift toward a more aggressive biological phenotype, underscoring the clinical relevance of monitoring proliferation indices even within the Luminal A subtype. While causality cannot be inferred, identification of a clinically actionable Ki-67 threshold may aid risk stratification and supports future research integrating molecular profiling to clarify mechanisms underlying temporal biological change.