Escalation and De-Escalation of Adjuvant Radiotherapy in Early Breast Cancer: Strategies for Risk-Adapted Optimization

Simple Summary Radiotherapy (RT) is a cornerstone in the adjuvant treatment of breast cancer. Continuous technical improvements allow better sparing of organs at risk compared to the past with a potential reduction of RT-related toxicity. Whereas prior trials focused on histopathological criteria, mainly T- and N-stage, biological parameters like endocrine responsiveness and proliferation helped to identify a low-risk subgroup in which omission of RT is an option. Ongoing trials are incorporating molecular markers and the response to neoadjuvant systemic therapy for additional risk stratification. De-escalation regarding volume (partial breast irradiation only-PBI) can be used in selected cases. Hypofractionated regimens should be standard. In contrast, the omission of axillary dissection in node-positive disease led to an escalation of regional RT, and RT for oligometastatic disease is becoming increasingly popular. Studies are ongoing to test if any axillary treatment can be omitted and which oligometastatic patients do really benefit from RT.Abstract Postoperative radiotherapy (RT) is recommended after breast-conserving surgery and mastectomy (with risk factors). Consideration of pros and cons, including potential side effects, demands the optimization of adjuvant RT and a risk-adapted approach. There is clear de-escalation in fractionation-hypofractionation should be considered standard. For selected low-risk situations, PBI only or even the omission of RT might be appropriate. In contrast, tendencies toward escalating RT are obvious. Preoperative RT seems attractive for patients in whom breast reconstruction is planned or for defining the tumor location more precisely with the potential of giving ablative doses. Dose escalation by a (simultaneous integrated) boost or the combination with new compounds/systemic treatments may increase antitumor efficacy but also toxicity. Despite low evidence, RT for oligometastatic disease is becoming increasingly popular. The omission of axillary dissection in node-positive disease led to an escalation of regional RT. Studies are ongoing to test if any axillary treatment can be omitted and which oligometastatic patients do really benefit from RT. Besides technical improvements, the incorporation of molecular risk profiles and also the response to neoadjuvant systemic therapy have the potential to optimize the decision-making concerning if and how local and/or regional RT should be administered.