VTCN1 encodes the protein B7-H4 and has been previously associated with immunotherapy response in breast cancer, particularly in HER2+ breast cancer.48 CDK12 has been shown to induce trastuzumab resistance and stimulate HER2 signalling.49 Likewise, RAC1 has been implicated in resistance to chemotherapy, radiotherapy, and targeted therapies, such as trastuzumab.50 This may suggest that HER2-targeted TKIs, alone or in combination with CDK12 or RAC1 inhibition, could be a more appropriate therapeutic strategy than trastuzumab for high CDK12- or RAC1-expressing HER2+ breast cancer. This evidence concerns the gene VTCN1 and breast cancer.