Clinical trials in the neoadjuvant setting have shown that patients with HR+ tumors have a significantly lower likelihood of achieving a pathologic complete response (pCR) when treated with HER2-targeted therapy plus chemotherapy than those with HR− tumors15,16,18–22, whereas in the advanced/metastatic disease setting, those with HER2+ tumors are significantly less responsive to ET than HER2− tumors17. Here, ERBB2 is linked to metastatic neoplasm.