Analysis of tumor samples from postmenopausal patients with stages II and III HR+ breast cancer treated on two-independent neoadjuvant endocrine therapy trials showed that HR+/HER2+ tumors had significantly higher histologic grade and Ki-67 and significantly less suppression of Ki-67 after treatment with tamoxifen or an aromatase inhibitor (AI) compared with HR+/HER2- tumors. This evidence concerns the gene HR and breast cancer.