ESR1 and neoplasm: In the CT-50 case, during Palbociclib-letrozole therapy, an acquired ESR1 mutation was detected 6 weeks earlier than true clinical progression was diagnosed by means of the CT, bone scan, and circulating tumor markers (note that the ESR1 mutation in the liver metastasis was detected at the time of disease progression, but in the primary tumor, no such alteration was verified); everolimus with exemestane was moderately effective, but chemotherapy could control the disease (note how sensitively ctDNA followed the disease status).