However, HER2-low and HER2-zero breast cancer differ not only in terms of HER2 protein expression level, but also in terms of estrogen receptor (ER) status, primary tumor volume, lymph node involvement, pathological complete response (pCR) rate after neoadjuvant chemotherapy (NAC), and disease-free survival (DFS) (11, 12). This evidence concerns the gene ESR1 and neoplasm.