ESR1 and breast carcinoma: To mimic the in vivo treatment conditions, MCF7 cells were treated with E2 (10−9M) and with two concentrations of E4: (i) 10−10M E4, mimicking the effect of the therapeutic dose in vivo, since it is the first concentration in vitro that did not increase breast cancer cell proliferation (Figure 4); (ii) 10−7M E4, corresponding to the supratherapeutic dose, since this concentration activated ERα signaling and increased breast cancer cell proliferation in vitro, similar to 10−9M E2 (Figure 4).