NOTCH4 and breast cancer: Moreover, an increase in Notch target genes (HEY1 and HES1) expression was observed in ALDH+/ER− BCSCs [129]; these results indicate that BCSCs and Notch4/HEY/HES gene signature predict acquired tamoxifen resistance and suggest that endocrine therapy in combination with JAG1/Notch4 inhibitors could overcome resistance in BC.