However, in patients with HER2 positive tumours that are IHC 2+ amplified, there is a significant impact of ER status on the response rate; 38% pCR rate in ER negative tumours compared to 15% in ER positive tumours, which may reflect the mixed effect of HER2 and ER pathway activation on BC growth and progression.41–43 When the analysis was limited to patients who had received chemotherapy and HER2 targeted therapy and the cohort was stratified based on ER expression, the response rate of Group 2 was not different to that of Group 1 tumours or of the combined Group 1 and Group 3 tumours. This evidence concerns the gene ERBB2 and neoplasm.