Study of CDK46 Inhibitors with Endocrine Therapy as Neoadjuvant Treatment for Early Hormone Receptor-Positive HER2-Negative Breast Cancer Using ctDNA to Guide Personalized Chemotherapy Decisions

What this Trial Is About

Breast cancer, particularly the hormone receptor-positive HR, HER2-negative subtype, accounts for about 70% of cases and remains a major cause of illness and death worldwide. This trial evaluates the use of circulating tumor DNA ctDNA to guide personalized treatment, aiming to reduce the need for toxic chemotherapy in early-stage, high-risk breast cancer patients. The study focuses on the impact of neoadjuvant therapy combining CDK46 inhibitors with endocrine therapy and explores whether ctDNA can help safely adjust post-surgery treatment. Participants receive 4 cycles of neoadjuvant therapy with a CDK46 inhibitor plus endocrine therapy. After surgery, treatment is tailored based on ctDNA status those who are ctDNA-negative continue CDK46 inhibitor with endocrine therapy for 2 to 3 years, while ctDNA-positive patients may receive optional adjuvant chemotherapy followed by the same CDK46 inhibitor and endocrine therapy. Premenopausal women additionally receive ovarian suppression using LHRH agonists. Some patients are randomly assigned to receive chemotherapy or not based on their ctDNA results and tumor markers. During the study, participants undergo ctDNA testing to monitor treatment response, along with assessments of tumor response, including pathological complete response and markers like Ki67. Researchers track safety by recording treatment-related adverse events and measure long-term outcomes such as event-free survival over three years. The study duration includes neoadjuvant therapy, surgery, and extended follow-up with personalized treatment adjustments based on ctDNA findings.

CDK4/6 Inhibitors Combined With Endocrine Therapy for Neoadjuvant Treatment