However, there were many conflicting results in the literature that need to be addressed [31,32,33,34,35,36,130], of which include the standardized measurements of the ER expression before adopting them as a useful biomarker, the mechanisms that underlie the controversy in the effect of hormone replacement therapy, the role of different estrogen and various ER in lung cancer cell proliferation, migration, and invasion, and the pathways involved in their interactions with other mediators. The gene discussed is ESR1; the disease is lung cancer.