Although first approved in the metastatic setting for hormone receptor–positive (HR+) breast cancers, current clinical trials in HR+ breast cancer, including PALLAS (NCT02513394), monarchE (NCT03155997), PENELOPE-B (NCT01864746), and NATALEE (NCT03701334), seek to study the potential utility of CDK4/6 inhibitors in nonmetastatic HR+ breast cancer. This evidence concerns the gene NR4A1 and breast cancer.