Breast cancer surgery in the era of genetic uncertainty: real-world outcomes in BRCA1/2 pathogenic variants and variants of uncertain significance

While pathogenic BRCA1/2 variants are strongly associated with bilateral mastectomy in breast cancer patients, surgical decision-making among VUS carriers appears largely independent of tumor biology or genetic subtype and is primarily influenced by age. These findings highlight substantial heterogeneity and potential overtreatment in the management of BRCA VUS carriers, underscoring the need for improved genetic counseling and standardized approaches to mitigate the impact of genetic uncertainty on clinical decision-making.