PI3K inhibitors have demonstrated encouraging preliminary activity in the treatment of metastatic breast cancer, with responses observed in patients with and without PIK3CA and PTEN alterations.1,2 Evidence for the activity of PI3K inhibitor–based therapy in breast cancer has been drawn from a phase I study in patients with hormone receptor (HR)–positive metastatic breast cancer.3 In this trial, patients received continuous (n = 20) or intermittent (five days on, two days off; n = 31) doses of buparlisib in combination with letrozole. The gene discussed is PIK3CA; the disease is breast cancer.