In patients with HER2-positive breast cancer treated with an anti-HER1/HER2 tyrosine kinase inhibitor, ctDNA analysis for HER2 amplification was associated with disease progression (4/6, 66.7%), whereas TP53 mutations (3/6, 50%) and PI3K/mTOR pathway alterations (3/6, 50.0%) were associated with disease resistance. The gene discussed is ERBB2; the disease is breast carcinoma.