ESR1 and breast cancer: Similar to clinical breast tumors, breast cancer cell lines are heterogeneous and can yield clonal populations of inherently tamoxifen resistant cells that are variably ER-dependent [45]; nevertheless, the fraction of S-phase cells in hormone-depleted or tamoxifen-treated cells under the in vitro conditions in this study was much higher than the frequency of emergence of aggressively growing colonies in tamoxifen-treated cultures [45].