| Sumario: | Simple Summary: HER2-positive (HER2+) breast cancer is a fast-growing type of breast cancer that can have poor outcomes if not treated effectively. Over the past year, results from many important clinical trials were released, leading to improvements in how this cancer is treated. Newer treatments, including antibody–drug conjugates, have contributed significant improvements in both early and advanced settings. Because of these changes, Research Excellence, Active Leadership Canadian Breast Cancer Alliance (REAL Alliance) updated its HER2+ treatment recommendations using a structured expert-consensus approach. The 2025 update reflects new evidence for HER2+ early-stage breast cancer, advanced (metastatic) disease, and cancer that has spread to the brain. It includes updated guidance on treatments given before and after surgery, as well as expanded recommendations on when and how to use antibody–drug conjugates in clinical practice. Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive subtype associated with a poor prognosis when not optimally treated. Over the past year, major advances—including results from DESTINY-Breast05, DESTINY-Breast09, DESTINY-Breast11, PATINA, and long-term APHINITY follow-up—have changed the treatment landscape regarding the place in therapy of antibody–drug conjugates and the optimal sequencing of systemic therapies. These developments prompted the need for updated evidence-informed consensus recommendations to support consistent, high-quality care across Canada. Research Excellence, Active Leadership Canadian Breast Cancer Alliance (REAL Alliance), comprising clinical-academic oncologists from across Canada and Breast Cancer Canada, updated its 2024 HER2+ recommendations through a modified Delphi process with up to three rounds of anonymous voting. Consensus was defined a priori as ≥75% agreement. This 2025 update incorporates new data in early-stage, metastatic, and central nervous system-involved disease, including revisions to neoadjuvant and adjuvant treatment pathways and expanded guidance on the clinical use of antibody–drug conjugates.
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