As previously mentioned, increased growth factor signaling (in particular the EGFR/HER2 pathway), the estrogen agonist activity of tamoxifen in breast cancer cells that express high levels of HER2, aberrant expression cell cycle regulators and lack of expression of ERα in breast cancer are factors that contributes to tamoxifen resistance [97,180–182]. The gene discussed is ESR1; the disease is breast carcinoma.