To test this hypothesis in human tumors without exposing patients to an mTORC1 inhibitor, we conducted a presurgical study in which patients with Stage I-III ER+/HER2- breast cancer were treated +/− the AI letrozole for 10-21 d to induce estrogen deprivation; the 10-21-day period allows time for maximal estrogen suppression and downstream changes in the levels of ER-regulated transcripts [27]. The gene discussed is ESR1; the disease is breast cancer.