Also, clinical observations have shown that estrogen receptor (ER)-positive breast cancer patients whose tumors harboring high SPHK1 expression are generally less sensitive to tamoxifen treatment; whereas increased levels of SPHK1 are often detected in ER-negative breast tumors that failed chemotherapy as compared to those complete respondents, suggesting SPHK1 expression confers drug resistance in breast cancer (Long et al., 2010a; Watson et al., 2010; Datta et al., 2014). This evidence concerns the gene ESR1 and breast cancer.