Accordingly, luminal A MCF-7 breast cancer cells, which are normally highly sensitive to tamoxifen in vitro, can overcome the anti-proliferative effects of tamoxifen when exogenously treated with the HER3 ligand heregulin (HRG) by enriching for the growth factor signaling gene set and activating a proliferative signature similar to that of tamoxifen-resistant ER+ luminal B-type tumors [11]. This evidence concerns the gene ESR1 and breast cancer.