Female patients age ≥50 years with clinical T1-4c, N0-1, ER+/HER2–<PUB4> breast cancer (2012–2021) were selected from the National Cancer Database (NCDB) and divided into three groups based on treatment: upfront surgery, neoadjuvant chemotherapy (NAC), or NET. This evidence concerns the gene ESR1 and breast carcinoma.