The DBCG-RT Natural trial, sponsored by the Danish Breast Cancer Cooperative Group, is a non-inferiority phase III clinical trial designed to compare the 5-year risk of local recurrence between partial breast irradiation versus no irradiation among women ≥60 years with unifocal, pT1N0M0, ER+/HER2− invasive ductal carcinomas treated with breast-conserving surgery. The gene discussed is ESR1; the disease is breast carcinoma.