In contrast, in the absence of TP53 mutation, acquired ESR1 mutations may play a predominant role under the selective pressure of endocrine therapy, particularly aromatase inhibitors that block production of estrogen, giving rise to ESR1 mutation-enriched metastatic lesions in approximately 30% of ER + metastatic breast cancers (Fig. 6). The gene discussed is CYP19A1; the disease is breast cancer.