Estrogen Receptor Mutations and Their Role in Breast Cancer Progression

Overview

Journal Breast Cancer Res

Specialty Oncology

Date 2015 May 1

PMID 25928204

Citations 49

Authors

Prasanna G Alluri

Corey Speers

Arul M Chinnaiyan

Affiliations

Soon will be listed here.

Abstract

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.

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References

Musgrove E, Sutherland R . Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer. 2009; 9(9):631-43. DOI: 10.1038/nrc2713. View

Asangani I, Dommeti V, Wang X, Malik R, Cieslik M, Yang R . Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014; 510(7504):278-82. PMC: 4075966. DOI: 10.1038/nature13229. View

Chumsri S, Howes T, Bao T, Sabnis G, Brodie A . Aromatase, aromatase inhibitors, and breast cancer. J Steroid Biochem Mol Biol. 2011; 125(1-2):13-22. PMC: 3104073. DOI: 10.1016/j.jsbmb.2011.02.001. View

Wardell S, Marks J, McDonnell D . The turnover of estrogen receptor α by the selective estrogen receptor degrader (SERD) fulvestrant is a saturable process that is not required for antagonist efficacy. Biochem Pharmacol. 2011; 82(2):122-30. PMC: 3109090. DOI: 10.1016/j.bcp.2011.03.031. View

Roychowdhury S, Iyer M, Robinson D, Lonigro R, Wu Y, Cao X . Personalized oncology through integrative high-throughput sequencing: a pilot study. Sci Transl Med. 2011; 3(111):111ra121. PMC: 3476478. DOI: 10.1126/scitranslmed.3003161. View

Baselga J, Campone M, Piccart M, Burris 3rd H, Rugo H, Sahmoud T . Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2011; 366(6):520-9. PMC: 5705195. DOI: 10.1056/NEJMoa1109653. View

Roop R, Ma C . Endocrine resistance in breast cancer: molecular pathways and rational development of targeted therapies. Future Oncol. 2012; 8(3):273-92. DOI: 10.2217/fon.12.8. View

Ellis M, Ding L, Shen D, Luo J, Suman V, Wallis J . Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 2012; 486(7403):353-60. PMC: 3383766. DOI: 10.1038/nature11143. View

. Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490(7418):61-70. PMC: 3465532. DOI: 10.1038/nature11412. View

10.

Recupero D, Daniele L, Marchio C, Molinaro L, Castellano I, Cassoni P . Spontaneous and pronase-induced HER2 truncation increases the trastuzumab binding capacity of breast cancer tissues and cell lines. J Pathol. 2012; 229(3):390-9. DOI: 10.1002/path.4074. View

11.

Kandoth C, Schultz N, Cherniack A, Akbani R, Liu Y, Shen H . Integrated genomic characterization of endometrial carcinoma. Nature. 2013; 497(7447):67-73. PMC: 3704730. DOI: 10.1038/nature12113. View

12.

Holohan C, Van Schaeybroeck S, Longley D, Johnston P . Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013; 13(10):714-26. DOI: 10.1038/nrc3599. View

13.

Li S, Shen D, Shao J, Crowder R, Liu W, Prat A . Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. Cell Rep. 2013; 4(6):1116-30. PMC: 3881975. DOI: 10.1016/j.celrep.2013.08.022. View

14.

Robinson D, Wu Y, Vats P, Su F, Lonigro R, Cao X . Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013; 45(12):1446-51. PMC: 4009946. DOI: 10.1038/ng.2823. View

15.

Toy W, Shen Y, Won H, Green B, Sakr R, Will M . ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013; 45(12):1439-45. PMC: 3903423. DOI: 10.1038/ng.2822. View

16.

Merenbakh-Lamin K, Ben-Baruch N, Yeheskel A, Dvir A, Soussan-Gutman L, Jeselsohn R . D538G mutation in estrogen receptor-α: A novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res. 2013; 73(23):6856-64. DOI: 10.1158/0008-5472.CAN-13-1197. View

17.

Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo A . Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res. 2014; 20(7):1757-1767. PMC: 3998833. DOI: 10.1158/1078-0432.CCR-13-2332. View

18.

Eberwine J, Sul J, Bartfai T, Kim J . The promise of single-cell sequencing. Nat Methods. 2014; 11(1):25-7. DOI: 10.1038/nmeth.2769. View

19.

Fuqua S, Wiltschke C, Zhang Q, Borg A, Castles C, Friedrichs W . A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions. Cancer Res. 2000; 60(15):4026-9. View

20.

Gorre M, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao P . Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001; 293(5531):876-80. DOI: 10.1126/science.1062538. View