Two studies, BOLERO-1 and BOLERO-3, reported the combined exploratory biomarker analysis results of molecular changes in MBC with HER2 overexpression and the curative effect of everolimus.167,168 The final result demonstrated that patients with PIK3CA mutation, PTEN deletion, or PI3K pathway activation of HER2-positive progressive breast cancer could acquire PFS improvement from everolimus.169,170. The gene discussed is PIK3CA; the disease is breast carcinoma.