Estrogen receptor mutations and their role in breast cancer progression.
Endocrine therapy is the mainstay of treatment in estrogen receptor-positive breast cancers and significantly reduces disease recurrence and breast cancer-related mortality. However, acquired resistance to therapy has been noted in nearly one-third of women treated with tamoxifen and other endocrine therapies. Mutations in the estrogen receptor have long been speculated to play a role in endocrine therapy resistance but have been rarely detected. However, recent studies utilizing next-generation sequencing on estrogen receptor-positive, metastatic clinical samples have revealed that recurrent ESR1 mutations are far more frequent than previously thought and may play an important role in acquired endocrine therapy resistance. Here we review recent advances in detection and characterization of ESR1 mutations in advanced, endocrine therapy-resistant breast cancers.
Department of Radiation Oncology, University of Michigan Medical School, 1500 E. Medical Center Drive, B2-C445 UH, Ann Arbor, MI, 48109-5010, USA. palluri@med.umich.edu.|Michigan Center for Translational Pathology, University of Michigan Medical School, 1400 E. Medical Center Drive, 5316 CCC, Ann Arbor, MI, 48109-5940, USA. palluri@med.umich.edu.
Prasanna G
PG
Alluri
Department of Radiation Oncology, University of Michigan Medical School, 1500 E. Medical Center Drive, B2-C445 UH, Ann Arbor, MI, 48109-5010, USA. cspeers@med.umich.edu.
Corey
C
Speers
Michigan Center for Translational Pathology, University of Michigan Medical School, 1400 E. Medical Center Drive, 5316 CCC, Ann Arbor, MI, 48109-5940, USA. arul@med.umich.edu.|Comprehensive Cancer Center, University of Michigan Medical School, 1400 E. Medical Center Drive, 5316 CCGC 5940, Ann Arbor, MI, 48109-5940, USA. arul@med.umich.edu.|Department of Pathology, University of Michigan Medical School, 1301 Catherine, M5240 Med Sci I, Ann Arbor, MI, 48109-5602, USA. arul@med.umich.edu.|Department of Urology, University of Michigan Medical School, 1500 E. Medical Center Drive, 3875 TC, Ann Arbor, MI, 48109-5330, USA. arul@med.umich.edu.|Howard Hughes Medical Institute, University of Michigan Medical School, 1500 E. Medical Center Drive, 5316 CCC, Ann Arbor, MI, 48109-5940, USA. arul@med.umich.edu.
Arul M
AM
Chinnaiyan
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D013629:Tamoxifen / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D013629:Tamoxifen