Tirzepatide Weight Loss for MRD+ Early Breast Cancer

The goal of this clinical trial is to learn if tirzepatide induced weight loss effects survival outcomes in high risk early breast cancer patients. The main questions it aims to answer are: 1. Does tirzepatide-induced weight loss lead to clearance of plasma ctDNA in the adjuvant setting in patients with obesity or overweight who have HR+, HER2-, N+ early breast cancer who are at high risk of recurrence, and 2. Does tirzepatide-induced weight loss prevent the development of overt metastatic disease and improve distant disease-free survival, in the two-year period following first detection of ctDNA in patients with obesity or overweight who have HR+, HER2-, N+ early breast cancer who are at high risk of recurrence. Researchers will assess clinical outcomes after the first 20 patients are enrolled and have taken tirzepatide for at least 6 months. If at least three of the first 20 evaluable patients demonstrate clearance of ctDNA on tirzepatide, or at least ten of the first 20 patients remain alive and free of distant metastatic disease during the two-year period following initial detection of ctDNA using the Kaplan-Meier method, an additional 28 ctDNA-positive patients will be enrolled. Patients will screen for ctDNA every 3 months for up to 3 years or until ctDNA positivity, whichever comes first. Once positive, they will undergo radiologic imaging to confirm the absence of frank metastatic disease. If confirmed, patients will receive tirzepatide once weekly for up to 2 years, visit the clinic monthly for the first 6 months, and every other month thereafter.