ESR1 and neoplasm: Exploration into the complexity of receptor signaling has identified that receptor crosstalk constitutes a fundamental mechanism of tumor resistance, and preclinical observations have confirmed that activation of ER and ErbB Family receptors, namely EGFR/HER2, on the tumor cell surface stimulates multiple intracellular signaling cascades, leading to cellular proliferation, survival and differentiation (Ullrich and Schlessinger 1990; Klapper et al. 2000).