ESR1 and breast cancer: Recently, the identification of an alternative ER, G protein coupled estrogen receptor (GPR30), which was identified as a membrane-associated receptor mediating rapid and nongenomic estrogenic effects, including transactivation of epidermal growth factor receptor (EGFR) and production of second messengers, such as cAMP, calcium, and inositol triphosphate in physiological and pathophysiological conditions, has provided a reasonable explanation for TAM resistance in breast cancer for the following reasons.