Unraveling emerging genes and their functional pathways in breast cancer susceptibility and progression

Breast cancer remains one of the leading causes of cancer-related morbidity and mortality among women worldwide. While mutations in BRCA1 and BRCA2 have long been recognized as key drivers of hereditary breast cancer, recent advances in genomic research have uncovered a growing set of additional genes such as PALB2, CHEK2, ATM, FANCM, and RAD51C—that contribute to breast cancer susceptibility. These genes are involved in critical molecular pathways, including homologous recombination DNA repair, cell cycle checkpoint control, apoptosis, and tumor suppression. Dysfunction in these pathways, often triggered by germline mutations, can lead to genomic instability, uncontrolled proliferation, and tumorigenesis. This review provides a comprehensive analysis of these emerging genetic factors, detailing their mechanisms of action, pathway interactions (e.g., BRCA–PALB2–RAD51 axis, ATM–CHEK2–p53 checkpoint signaling), and their impact on both familial and sporadic forms of breast cancer. We also discuss the clinical relevance of integrating multi-gene panels and polygenic risk scores (PRS) into personalized risk assessment and prevention strategies. By highlighting the molecular pathways disrupted by these gene mutations, we emphasize the importance of expanding genetic testing beyond BRCA1/2. A deeper understanding of these pathways not only refines risk stratification but also opens new avenues for targeted therapy, early detection, and tailored clinical management of breast cancer.