However, these mAb treatments showed side effects such as ocular and neuro-ophthalmic toxicity, skin toxicities with different severities (from mild lichenoid reaction to severe toxic epidermal necrolysis), increased risk factors in development of hypogammaglobulinemia and infections (post-rituximab), and increased cumulative incidence of breast cancer brain metastases after HER2-directed therapy (trastuzumab)21–24. This evidence concerns the gene ERBB2 and breast cancer.