Despite research suggesting that mutation in ESR1 is an acquired mechanism of resistance to endocrine therapy (ET), the impact of this mutation on therapy response in primary breast cancer remains unclear. To better understand this impact, study investigators analyzed more than 3,200 real-world and population-based early-stage primary breast cancers. Tissues sampled from initial diagnosis, prior to any treatment, were analyzed for the presence of ESR1 mutations using RNA sequencing. ESR1 resistance mutations were identified in 0.9% of cases, of which 1.1% were estrogen receptor-positive. In estrogen receptor-positive disease, presence of ESR1 mutation was significantly associated with poor relapse-free (RFS) and overall survival (OS), and it predicted poor RFS and OS within the patient group who received ET. “We confirm for the first time that such early mutations predict eventual resistance to standard hormone therapy in the adjuvant setting,” write the study authors.