Navigating the New Frontier: Combining Radiotherapy and New Systemic Therapies in Breast Cancer

The revolution in targeted systemic therapies and immunotherapy has profoundly changed the management of breast cancer, raising major questions regarding their safe combination with radiotherapy. We conducted a narrative literature review aiming to provide a critical and hierarchical analysis of current recommendations, including the 2024 international ESTRO consensus, by contextualizing them within the broader scientific landscape. The results, presented by therapeutic class, are illustrated with summary tables and a proposed decision-making algorithm. The discussion addresses clinical and translational challenges, including potential biological interactions, the importance of pharmacokinetics, and the crucial need for predictive biomarkers. We conclude that the integration of radiotherapy and systemic treatment must evolve from an empirical and cautious approach towards a personalized strategy, guided by mechanistic understanding and robust prospective data, within the framework of strengthened multidisciplinary collaboration.