Abstract
BACKGROUND: Chromosomal instability (CIN) and clonal heterogeneity (CH) are fundamental hallmarks of breast cancer that drive tumor evolution, disease progression, and therapeutic resistance. Understanding the mechanisms underlying these phenomena is essential for improving cancer diagnosis, prognosis, and treatment strategies. METHODS: In this review, we provide a comprehensive overview of the biological processes contributing to CIN and CH, highlighting their molecular determinants and clinical relevance. RESULTS: We discuss the latest advances in detection methods, including single-cell sequencing and other high-resolution techniques, which have enhanced our ability to characterize intratumoral heterogeneity. Additionally, we explore how CIN and CH influence treatment responses, their potential as therapeutic targets, and their role in shaping the tumor immune microenvironment, which has implications for immunotherapy effectiveness. CONCLUSIONS: By integrating recent findings, this review underscores the impact of CIN and CH on breast cancer progression and their translational implications for precision medicine.