Germline BRCA2 mutations foster resistance to CDK4/6 inhibitors in breast cancer

While CDK4/6 inhibitors have revolutionized the management of patients with breast cancer, the clinical benefits of these agents remain limited by resistance mechanisms. Recent findings demonstrate that germline BRCA2 mutations foster resistance to CDK4/6 inhibitors via RB1 loss-of-function alterations that (in some cases) are acquired through persistent homologous recombination defects.