We further showed the clinical relevance of increased HRG expression in TKI-resistant tumor cells in a large breast cancer dataset (n = 204) of women with HER2+ breast cancers where increased HRG expression was an independent predictor for a significantly poorer clinical outcome (recurrence-free survival) compared with women whose tumors expressed moderate to low levels of HRG (P < 0.0036). This evidence concerns the gene ERBB2 and breast cancer.