CDK4/6 inhibitor rechallenge therapy in advanced breast cancer.

Hormone receptor (HR)-positive is the most common subtype in female breast cancer (BC) patients, and endocrine therapy (ET) is the primary treatment for HR-positive BC. Clinical studies have confirmed that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with ET can significantly prolong the progression-free survival (PFS) of advanced BC patients. Consequently, the combination of CDK4/6 inhibitors and ET has been established as a first-line treatment for advanced HR-positive BC or a standard treatment following ET progression. However, the regimen after CDK4/6 inhibitor treatment failure remains highly controversial, and the reported clinical outcomes of CDK4/6 inhibitor rechallenge are inconsistent. Preclinical studies have collected evidence suggesting that multiple mechanisms may contribute to intrinsic or acquired resistance to CDK4/6 inhibitors. Future research should further investigate the translational relationship between resistance mechanisms and clinical efficacy, and identify biomarkers to screen the benefit population from CDK4/6 inhibitor rechallenge therapy, developping individualized treatment strategies.