To determine the effects of physiologic E2 and P4 exposures as they occur in premenopausal women during menstrual cycles on ER + breast carcinogenesis in vivo, we engrafted immunocompromised NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) females by direct injections into the milk ducts with widely used ER + BC cell lines and fresh patient tumor-derived cells, genetically labeled with a dual luciferase-RFP reporter (Fig. 1a). The gene discussed is ESR1; the disease is neoplasm.