Indeed, preclinical studies from our laboratory [9-12] and other investigators [13,14]) have previously shown that long term estrogen deprivation of ER-positive MCF-7 breast cancer cells causes them to lose their dependency on estradiol for proliferation, which recapitulates acquired resistance to aromatase inhibitors in postmenopausal women, and that these AI-resistant breast cancer cells paradoxically undergo apoptosis in the presence of estradiol [10-12,15,16]. This evidence concerns the gene ESR1 and breast cancer.