Previously, several in vitro studies showed that tamoxifen and 4-OHT can cross-talk with other signaling pathways such as the p38/MAPK and the SAPK/JNK pathways, and induce apoptosis in both ER-positive breast cancer cells such as MCF7 and ER-negative cells such as MDA-MB-231 [33], [34], [35], [36]. Here, ESR1 is linked to breast cancer.