Summary

Genomic analysis and molecular profiling identified mutations and translocations in ER+ breast cancer that are targets for genome-directed therapeutics. ESR1 mutations and translocations contribute to endocrine therapy resistance. Novel pharmacologic approaches have successfully treated ESR1 Y537 mutation-driven resistance, mutant HER2 tumors, and wild-type RB and TP53 tumor suppressor function in preclinical and clinical work.