The effect and safety of CDK4/6 inhibitors combined endocrine therapy on HR+, HER2-breast cancer: a meta-analysis of randomized controlled trials

Abstract

Despite favourable improvements in overall survival in HR+, HER2-BC after ET, 20% of patients will develop recurrent metastases, and patients with high-risk clinical or pathologic features are at higher risk of recurrence [14][15][16]. Moreover, patients may develop intrinsic or acquired endocrine resistance and thereby resistance during first-line or multiple lines of ET [17,18]. Researchers have found a variety of resistance pathways [21][22][23], based on their investigation of the potential endocrine resistance mechanisms of HR+, HER2-BC [19,20]. Among them, cyclin-dependent kinase4/6 (CDK4/6) promotes retinoblastoma (Rb) protein hyperphosphorylation [24,25], which leads to the transition of the cell cycle from the G1 to S phase [26,27]. This critical Rb checkpoint is involved in endocrine resistance in BC [28]. Therefore, researchers developed a series of CDK4/6 inhibitors (CDK4/6i): palbociclib, ribociclib, and abemaciclib [29][30][31].