Efficacy, Safety, and Biomarkers of Neoadjuvant Dalpiciclib (CDK4/6 inhibitor) plus Aromatase Inhibitors in Operable HER2‐Negative Luminal B Breast Cancer: A Prospective, Single‐Center, Single‐Arm, Phase II Trial (DANCER)

ABSTRACT Dalpiciclib, a cyclin‐dependent kinase 4/6 (CDK4/6) inhibitor, has demonstrated significant clinical activity and manageable safety in advanced luminal breast cancer, yet its neoadjuvant value remains unestablished. The single‐arm, phase II DANCER trial (NCT05640778) is the first to evaluate circulating tumor DNA (ctDNA)‐guided neoadjuvant CDK4/6 inhibitor therapy in patients with operable human epidermal growth factor receptor 2 (HER2)‐negative luminal B breast cancer, a subtype with poor chemotherapy response and unmet neoadjuvant needs. Thirty patients received dalpiciclib plus aromatase inhibitors (DAL‐AI) with ctDNA monitoring and multiomics profiling. At week 2, 26 (86.7%) patients achieved complete cell cycle arrest (primary endpoint). By surgery, 60.0% had partial response; breast pathological complete response and residual cancer burden 0–I rates were 6.7 and 3.3%, respectively. Treatment was well tolerated, with the most common grade ≥3 adverse events being neutropenia and leukopenia. Candidate predictive biomarkers included ctDNA clearance, GSTM1 copy number, MammaPrint index, plasma CCL4/CCL19 levels, and tissue pRb/CDK4 expression. A novel baseline response index combining CCL4 and pRb showed excellent predictive performance and stratified patients by likelihood of clinical benefit, with ctDNA dynamics further refining stratification. These findings support DAL‐AI as a promising neoadjuvant option and highlight the value of biomarker‐guided strategies for treatment optimization.