Personalized approaches to breast radiotherapy: strategies for treatment refinement

Radiotherapy (RT) is a crucial component of the adjuvant treatment of breast cancer that often follows breast conservation or mastectomy to further reduce the risk of local recurrence. As outcomes improve and our understanding of disease biology advances, interest is growing in de-escalating RT to minimize the treatment burden and side effects while maintaining oncologic outcomes. This review examines the evidence and summarizes the results of ongoing trials evaluating RT de-escalation strategies in breast cancer. We discuss hypofractionation and ultrahypofractionation for whole breast irradiation, showing efficacy comparable with that of conventional fractionation with improved convenience. The role of accelerated partial breast irradiation is explored, with an emphasis on its benefits and the importance of patient selection. We review data supporting omission of RT in selected patients with low-risk, early-stage disease, particularly older women with hormone receptor-positive disease. Ongoing research into biomarker-guided RT de-escalation is addressed, including trials using genomic assays and immunohistochemistry. Emerging data on RT de-escalation in HER2-positive and triple-negative breast cancers are discussed. Finally, we explore de-escalation strategies for locally advanced disease, including hypofractionation for post-mastectomy RT and potential omission of regional nodal irradiation after neoadjuvant chemotherapy for those with an excellent response. These strategies may allow more personalized approaches to RT, potentially improving quality of life without compromising oncologic outcomes.