Guidance for Canadian Breast Cancer Practice: National Consensus Recommendations for the Systemic Treatment of Patients with HER2+ Breast Cancer in Both the Early and Metastatic Settings (2025 Update)

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.