Negative feedback regulation is commonly found in endocrine systems and demonstrated by a decrease in ERα in response to E2 treatment in MCF‐7 breast cancer cells (Saceda et al., 1988) as well as in human internal mammary arteries, where ERα is downregulated along with ERβ and GPER (Haas et al., 2007). This evidence concerns the gene ESR2 and breast carcinoma.