Upregulated expression levels of the membrane-associated glycoprotein MUC4 masked the trastuzumab-binding epitope of HER2 and hindered the anti-proliferative and antibody-dependent cell-mediated cytotoxicity effects of trastuzumab; in addition, MUC4 expression contributed to T-DM1 resistance.[148,149] Clinically, based on DNA sequencing data from tumor tissue and peripheral blood, it has been observed that breast cancer patients with HER2 amplification and concurrent CDK12 amplification tend to exhibit a lower response to anti-HER2 therapy.[150]. This evidence concerns the gene MUC4 and breast carcinoma.