As an example of this multilayered complexity, a study of Chinese patients with breast cancer (which also included reanalysis of the MSK-BREAST, MutHER, and SUMMIT cohorts for verification) found that HER2-positive tumors with TP53 co-mutation had reduced sensitivity to HER2 mAb regimens (trastuzumab, trastuzumab plus pertuzumab, and trastuzumab plus chemotherapy) but were sensitive to the TKI pyrotinib, whereas HER2-negative tumors with ERBB2 mutation and TP53 co-mutation were insensitive to pyrotinib (41, 42). This evidence concerns the gene TP53 and breast cancer.