In the United States, 70% of breast cancers are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, and up to one fourth of patients will present with locally advanced disease.1,2 Neoadjuvant chemotherapy (NACT) and neoadjuvant endocrine therapy (NET) often are used to downstage locally advanced tumors and/or allow for breast-conserving surgery (BCS) among patients with early-stage, HR-positive/HER2-negative breast cancer that may otherwise require mastectomy. The gene discussed is NR4A1; the disease is breast cancer.