In a treatment-naive tumor, HER2 might be heterogeneously amplified, with PIK3CA mutation occurring more commonly in HER2-negative rather than HER2-positive cells, which makes a tumor with low HER2 expression (as observed in tumors with greater HER2 heterogeneity) more likely to also show a PIK3CA mutation. The gene discussed is ERBB2; the disease is neoplasm.