ESR1 and cancer: Unlike other metastatic signatures, which include genes functionally critical for the host organ (for example, the bone metastasis signature44 encodes proteins that alter the bone tissue environment to foster the formation of osteolytic bone lesions), the lung metastasis signature (LMS)36 is less specific to the lung microenvironment and rather promotes general features of aggressive growth and invasiveness in the cancer cells such as ER- status, a Rosetta-type poor prognosis signature23, and a basal-like phenotype.