In conclusion, our data suggested that BCSCs from HER2-negative breast cancer cells contributed to HER2-mediated radioresistance and HER2 subtype conversion from the primary HER2-negative tumor during disease progression, and that serum HER2 testing could be a clinical method to select the patients with HER2-negative advanced breast cancer that are suitable for HER2-targeted therapy. Here, ERBB2 is linked to breast cancer.