The switch from estrogen/ER-mediated tumorigenesis to SPHK1/S1P/EGFR-activated tumor growth has been regarded as important mechanism for acquiring endocrine resistance in ER-positive breast cancer (Sukocheva and Wadham, 2014; Maczis et al., 2016; Maczis et al., 2018). The gene discussed is MBTPS1; the disease is neoplasm.