Although the majority of BRCA2 and PALB2-associated breast cancers and 20% of BRCA1-associated breast cancers are hormone-receptor positive, human epidermal growth factor receptor negative (ER + HER2-), germline pathogenic variant carriers tend to have highly proliferative ER + HER2- tumors with markedly elevated 21-gene recurrence scores, for which chemotherapy is also recommended [6–8]. The gene discussed is ESR1; the disease is breast carcinoma.