This latter factor emerged clearly in the neo-adjuvant setting, when results of the NEO-ALTTO and NEO-SPHERE trials, evaluating neoadjuvant taxanes with anti HER2 treatments in HER2-positive patients, showed a clear reduction in pCR when the tumor co-expressed HRs, mirrored by very high pCR in HER2-positive/HRs negative tumors [30, 31]. This evidence concerns the gene ERBB2 and neoplasm.