Altogether, these results demonstrate that the structure of an angular estrogen, in particular the presence or absence of a free hydroxyl in para-position can affect the conformational stability of the TPE : ER complexes that, in turn, affects the ability of H12 to “close” and bind the co-activators and produce a full agonist effect, such as estrogen-induced apoptosis in LTED breast cancer cells. This evidence concerns the gene ESR1 and breast cancer.