In aggregate, these findings support the broad clinical relevance of GEM models for tumor dormancy and recurrence, and suggest that they are likely informative for the biology of residual tumor cells that survive selective pressures imposed by either targeted therapy or the microenvironment, and in a manner that is not restricted to ER+ versus ER-negative human breast cancers or to local versus distant sites of recurrence. This evidence concerns the gene ESR1 and breast cancer.