The next generation of TKIs including afatinib (Soria et al., 2015; Park et al., 2016; Paz-Ares et al., 2017), dacomitinib (Wu et al., 2017; Mok et al., 2018) and neratinib (Chan 2016; Chan et al., 2021) are irreversible pan-HER2 inhibitors (EGFR, HER2 and HER4), with afatinib and dacomitinib approved for non-small cell lung cancer (NSCLC) while neratinib approved for breast cancers. The gene discussed is ERBB2; the disease is breast carcinoma.