Pre-Adaptive States and Evolutionary Trajectories in Breast Cancer Drug Resistance: From Drug-Tolerant Persisters to Clonal Evolution

Drug resistance is a major cause of treatment failure in breast cancer, yet mutation-centered models do not fully explain delayed resistance, reversible tolerance, or re-sensitization after treatment interruption. Here, we synthesize recent findings in drug-tolerant persister (DTP) biology, clonal evolution, and tumor ecosystem dynamics to propose a breast cancer-focused Resistance Continuum as a conceptual framework for organizing the transition from initial therapy to stable resistance across