ESR1 and neoplasm: Notable cases include an ERBB2 amplification in a tumor with a pre-existing ERBB2L869R activating mutation, tumors in which the only acquired or enriched alterations were in the ER pathway (ESR1H524L, ESR1D538G, GATA3- 412fs), and a clonal BRAFV600E activating mutation in a tumor with concurrent ER loss (no activating BRAF mutations were reported in several previous HR + /HER2- MBC studies4,5,11,12,17 and the two reported in Razavi et al.16 were subclonal).