ESR1 and invasive breast carcinoma: We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER+/HER2− grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1–2 or T3–4, cN0–2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.