The Role of BRCA۱ and BRCA۲ Mutations in Breast Cancer: DNA Repair Deficiency and Therapeutic Implications

BRCA۱ and BRCA۲ are high-penetrance tumor suppressor genes that play critical roles in maintaining genomic stability through homologous recombination repair (HRR), cell cycle regulation, and apoptosis. Germline mutations in these genes are strongly associated with hereditary breast and ovarian cancer (HBOC) and represent a major cause of homologous recombination deficiency (HRD). HRD impairs the accurate repair of DNA double-strand breaks, resulting in genomic instability and increased susceptibility to breast cancer.This review summarizes current evidence regarding the biological functions of BRCA۱ and BRCA۲, their involvement in DNA repair pathways, and the relationship between BRCA-associated HRD and breast cancer development. In addition, the clinical significance of BRCA and HRD testing, as well as the therapeutic applications of targeted treatments, are discussed. Recent studies have demonstrated that HRD-positive tumors are more sensitive to platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors, providing new opportunities for personalized treatment strategies. In conclusion, BRCA۱ and BRCA۲ mutations play a central role in breast cancer pathogenesis by disrupting DNA repair mechanisms and promoting genomic instability. Improved understanding of HRD and the development of targeted therapies have enhanced risk assessment and treatment selection, highlighting the growing importance of personalized medicine in breast cancer management

کلیدواژه ها:

BRCA۱ ، BRCA۲ ، Breast Cancer ، Homologous Recombination Deficiency(HRD) ، DNA Repair ، PARP Inhibitors ، Personalized Medicine