Unconjugated ISG15 increases major histocompatibility complex (MHC) expression on the surface of breast cancer cells exhibiting anti-tumour properties [57] while elevated ISG15 levels are associated with adverse factors in breast cancer, such as higher histological grade, lymphovascular invasion, larger tumour size, hormone receptor negativity, and Human epidermal growth factor receptor 2 (HER2) positivity [66]. This evidence concerns the gene ERBB2 and breast carcinoma.