The Role of TP53 Gene Mutations in the Pathogenesis of Breast Cancer

Abstract

TP53 is a pivotal tumor suppressor gene that maintains genomic integrity by regulating DNA repair, cell cycle arrest, senescence, and apoptosis. It encodes the p53 protein, often dubbed the "guardian of the genome." TP53 mutations are among the most common genetic alterations in human cancers, particularly in aggressive breast cancer subtypes such as triple-negative and HER2-positive tumors. These mutations frequently lead to loss of tumor-suppressive functions or gain of oncogenic properties, promoting tumor progression, metastasis, and therapy resistance. This narrative review explores the molecular mechanisms by which TP53 mutations drive breast cancer pathogenesis and therapeutic failure. It emphasizes the functional consequences of distinct mutation types, their correlation with tumor behavior, and their relevance as prognostic indicators. By synthesizing recent findings, this review underscores the potential of TP53 mutations as predictive biomarkers and therapeutic targets in advancing personalized breast cancer treatment.