ESR1 and metastatic neoplasm: Our results are in line with the assumption that transcriptional activation by ER in metastatic disease could be pertinent to endocrine sensitivity in the context of wild-type ESR1, but could be active yet resistant to endocrine treatment if predominantly due to mutant ESR1. However, a far larger experience of samples data and treatment outcomes will be necessary to understand whether this is a real observation and whether the proportion of mutant ESR1 is relevant to outcomes.