For this purpose, we use sequencing data obtained in 70 ER + /HER2– MBC patients by both the Oncomine breast panel (Thermofisher) and the Qiaseq Human Breast Cancer Panel (Qiagen) to optimize the calling of somatic variants beyond the well-known hotspot regions by a machine learning algorithm using the well-established Oncomine panel9–12 as gold standard. The gene discussed is ESR1; the disease is breast cancer.