HERizon-Breast: A ctDNA-Guided Adaptive Study of Sequential Anti-HER2 Therapies and CNS Prophylaxis to Induce Long-Term Remission

This study tests a strategy of sequentially switching between different anti-HER2 targeted treatments (drugs that attack a protein called HER2 on breast cancer cells) guided by a blood test called ctDNA (which detects cancer DNA circulating in the bloodstream) for patients with HER2-positive advanced breast cancer that has spread to other organs. The study also includes a brain-protection treatment strategy, since HER2-positive breast cancer commonly spreads to the brain. **You may be eligible if...** - You are 18 or older with confirmed HER2-positive (IHC 3+) advanced or metastatic breast cancer - Your cancer was metastatic from the start (stage IV at diagnosis) - You have never received anti-HER2 therapy or any prior systemic treatment for breast cancer - You have measurable disease on imaging and are fit enough to be considered for surgery after treatment - You are in good physical condition (ECOG 0–1) **You may NOT be eligible if...** - You have HER2-low positive disease (IHC 1-2+ with positive gene test only) - You have previously received any anti-HER2 or anti-cancer treatment for breast cancer - You have known brain metastases at the start of the study - You have a history of severe lung inflammation, Grade 3 or higher nerve damage, or a serious cardiovascular condition - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.