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).

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.