When we stratified the Nottingham BC IHC cohort based on the LVI and HER2 status, high protein expression of ISG15 was associated with poor BCSS in the LVI-positive survival cases (p = 0.005, Fig. 3b), and in the HER2-positive survival cases (p = 0.046; Fig. 3c) subgroups, similar of poor survival trend were observed for LVI-negative survival cases and HER2-negative survival cases, but it did not reach statistical significant (p > 0.05, Supplementary Fig. 2E and F, respectively). This evidence concerns the gene ERBB2 and breast cancer.