When the parental MCF7 and T47D cells, and their tumorsphere cells were transfected with a ERE containing luciferase reporter plasmid and treated with or without estrogen, we found that estrogen-induced transcription activities of ER-α66 were dramatically reduced in tumorsphere cells compared to parental cells (Figure 7D), indicating the genomic estrogen signaling mediated by ER-α66 is attenuated in ER-positive breast cancer stem/progenitor cells. This evidence concerns the gene ESR1 and breast cancer.