However, the use of tamoxifen has been confirmed to be involved in the upregulation of ERα36, SPhk1 (sphingosine kinase 1), and S1P (sphingosine-1-phosphate), which further activates downstream signaling pathways and causes drug resistance (Maczis et al., 2018), while the inhibition of ERα36 is beneficial to restore the sensitivity of breast cancer cells to tamoxifen. This evidence concerns the gene SPHK1 and breast cancer.