EGFR and lung adenocarcinoma: For example, EGFR exon 20 insertion is observed in 3% of patients with lung adenocarcinoma and 9% of patients with EGFR mutations, leading to third-generation EGFR-TKI resistance.35 Deletions of exon 16 of human epidermal growth factor receptor 2 (HER2) splice variant (Δ16HER2) lead to primary resistance to lapatinib in breast cancer cell lines.