However, both immediate in vitro (1 h) and long-term in vivo reduction in the protein expression of Akt kinase, which is implicated in tumor progression and drug resistance [20, 21], in Z-endoxifen-treated MCF7LR tumors, suggest that Z-endoxifen may have additional roles beyond targeting ERα in ER+ breast cancer. Here, ESR1 is linked to breast carcinoma.