Tsai et al., reported MKK3 tumor suppressor functions in estrogen receptor-positive (ER+) breast cancer MCF7 and BT474 lines [40], demonstrating that activation of the Rac1-MKK3/6-p38MAPK signaling is required for Connexin 43 (Cx43) protein reduction induced by Fulvestran and Tamoxifen treatments in ER+ cells inhibiting migration and invasion. This evidence concerns the gene ESR1 and breast cancer.