Understanding the complexity of the disease is urgently required to find personalized therapy for various kinds (i.e., estrogen receptor (ER)-positive and ER-negative; progesterone receptor (PR)-positive and PR-negative; human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative; and triple-negative (ER-PR-HER2-negative)) of breast cancer, as there is no single target for treating such a complex malignancy. The gene discussed is ESR1; the disease is breast cancer.