EXamining PErsonalised Radiation Therapy for Low-risk Early Breast Cancer

Radiation therapy (RT) after breast conserving surgery to improve local control and survival is the current standard of care for patients with early breast cancer. However, breast cancer is a heterogeneous disease, and the absolute benefit of RT in individual patients varies substantially. Thus, a pressing priority in contemporary breast cancer management is to tailor RT utilisation to the individual recurrence risks by identifying patients who are unlikely to benefit from RT, thereby avoiding the morbidity and costs of over-treatment. It is recognised that selected patients with early breast cancer are unlikely to derive benefits from RT after breast conserving surgery. However, randomised trials have not consistently identified patients who may safely omit RT using conventional clinical-pathologic characteristics. Breast cancer intrinsic subtypes distinguished by gene expression profiling are shown to be associated with distinct clinical outcomes. There is substantial evidence supporting the clinical validity of multigene assays including the PAM50-based Prosigna Assay that identifies intrinsic subtypes and generates a Risk of Recurrence score (ROR) to quantify individual risks of distant relapse. Multigene assays are increasingly integrated into clinical practice to inform chemotherapy decision, highlighting their substantial practice changing potential in personalising the use of RT for early breast cancer. A recent analysis of archived tumour specimens of 1,308 patients with early breast cancer has shown significant associations between local recurrence risk and the PAM50-defined intrinsic subtypes and ROR score. EXPERT presents a unique opportunity of clinical and public health importance to optimise personalised local therapy for early breast cancer through precise, individualised quantification of local recurrence risk to identify low-risk patients for whom RT after breast conserving surgery may be safely omitted.