2026 Key European Guideline Changes for Metastatic Breast Cancer and Their Impact on Practice—Commentary based on a virtual focus group

(236 words) The treatment landscape for metastatic breast cancer continues to evolve rapidly, driven by advances in targeted therapies and biomarker-directed treatment decisions. The European Society for Medical Oncology Living Guidelines framework allows for timely updates reflecting emerging evidence, with the 2026 update representing significant changes across all breast cancer subtypes. An expert panel was assembled to discuss key modifications from the Living Guidelines version 1.2 to the 2026 update, examining supporting clinical trial evidence and practice implications. In hormone receptor (HR)-positive, HER2-negative disease, guidelines now distinguish endocrine-sensitive from endocrine-resistant populations, with mandatory PIK3CA testing in the latter and expanded biomarker-driven second-line options. For HER2-positive disease, the antibody-drug conjugate (ADC) trastuzumab deruxtecan plus pertuzumab emerges as a first-line option alongside the established taxanes-trastuzumab-pertuzumab regimen, with selection guided by disease characteristics and prior therapy. Maintenance options have also expanded, including tucatinib added to dual HER2-targeted therapy or palbociclib added to HER2-targeted therapy and endocrine therapy for HR-positive/HER2-positive disease. In triple-negative breast cancer, ADCs now move into first-line therapy for both programmed death-ligand 1 (PD-L1)-positive and PD-L1-negative/immunotherapy-ineligible populations. These advances create new implementation challenges, including comprehensive biomarker testing requirements, adverse event management necessitating multidisciplinary collaboration, and educational needs spanning the entire healthcare team. This article synthesizes expert perspectives on navigating these guideline changes, addressing barriers, and identifying unanswered questions. Successful guideline implementation requires coordinated efforts in education, infrastructure development, and adaptive strategies tailored to regional resources and expertise.