Taselisib plus letrozole have shown clinical benefit as a neoadjuvant treatment in postmenopausal women with ER-positive, HER2 negative early-stage I–III resectable breast cancer in randomized phase II LORELEI trial with better ORR of 50% in the taselisib-letrozole group vs. 39% in the placebo-letrozole group (odds ratio 1.55, 95% CI 1.0–2.38; p = 0.033) with improved ORR of 56% among PIK3CA-mutated patients [125]. The gene discussed is ESR1; the disease is breast cancer.