ESR1 and breast cancer: Conversely, if the patient presents with multiple metastatic sites from a previous ERα− BC, and there is proven ERα positivity in one biopsied site, ET plus CDK 4/6 inhibitor combination could be proposed as a first-line therapeutic option (with the exception of ongoing or pending visceral crisis), but then it should be replaced by cytotoxic chemotherapy or other treatment options if one or more metastatic sites undergo progression at disease re-evaluation.