Moreover, the recent NeoPAL trial which evaluate the efficacy of letrozole and cyclin-dependent kinase 4/6 inhibitors (CDKi) palbociclib versus chemotherapy as neoadjuvant therapy of high-risk ER-positive, HER2-negative breast cancer showed that letrozole combined with palbociclib was associated with poor pathological response of chemotherapy, and had a very similar ultrasound response rate with chemotherapy (55.5% vs. 53.3%) [8]. Here, ESR1 is linked to breast cancer.