Austrian treatment algorithms 2025: CDK 4/6 inhibitors in the adjuvant therapy of HR+/HER2− early breast cancer

Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC) represents the most common breast cancer subtype, with relevant recurrence risks despite optimal endocrine therapy (ET) and locoregional treatment. Long-term data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) demonstrate that recurrence risk remains substantial, with outcomes strongly influenced by nodal burden, tumor size, and biological parameters.Advances in systemic therapy, including optimized endocrine strategies, chemotherapy, bone-modifying agents, PARP inhibitors for patients harboring germline BRCA 1/2-mutations, have significantly improved survival, yet recurrence remains a clinically relevant challenge, including for node-negative patients harboring additional biological risk features.The introduction of adjuvant CDK4/6 inhibitors represents an important therapeutic development. Abemaciclib (monarchE) has demonstrated sustained improvements in invasive disease-free survival (IDFS), distant relapse-free survival (DRFS), and a statistically significant overall survival (OS) benefit at 7 years. Ribociclib (NATALEE) demonstrated statistically significant IDFS improvement across a broader clinical risk spectrum, including selected node-negative disease.However, these advances must be considered in the context of distinct toxicity, treatment burden, and substantial additional healthcare system costs. Although emerging evidence supports treatment intensification with CDK4/6 inhibitors in certain settings, uncertainty persists regarding which patient subgroups derive sufficient benefit to justify routine use from both a clinical and health-economic perspective.Further clarification is expected from ongoing randomized studies and real-world evidence, as this paper aims to provide a structured, evidence-based overview of the current standard of knowledge and to support Austrian breast cancer specialists in navigating treatment decisions regarding adjuvant CDK4/6 inhibitor use.