International Journal of Cancer Management

Published by: Kowsar

Are Estrogen Receptor Genomic Aberrations Predictive of Hormone Therapy Response in Breast Cancer?

Sanaz Tabarestani 1 , Marzieh Motallebi 1 and Mohammad Esmaeil Akbari 1 , *
Authors Information
1 Cancer Research Center, Shahid Beheshti Univeristy of Medical Sciences, Tehran, IR Iran
Article information
  • Iranian Journal of Cancer Prevention: August 2016, 9 (4); e6565
  • Published Online: August 13, 2016
  • Article Type: Review Article
  • Received: April 28, 2016
  • Revised: May 21, 2016
  • Accepted: August 6, 2016
  • DOI: 10.17795/ijcp-6565

To Cite: Tabarestani S, Motallebi M, Akbari M E. Are Estrogen Receptor Genomic Aberrations Predictive of Hormone Therapy Response in Breast Cancer?, Int J Cancer Manag. 2016 ; 9(4):e6565. doi: 10.17795/ijcp-6565.

Copyright © 2016, Iranian Journal of Cancer Prevention. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Context
2. Evidence Acquisition
3. Results
4. Conclusions
  • 1. GLOBOCAN . International Agency for Research on Cancer. 2012;
  • 2. Nadji M, Gomez-Fernandez C, Ganjei-Azar P, Morales AR. Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5,993 breast cancers. Am J Clin Pathol. 2005; 123(1): 21-7[PubMed]
  • 3. Beatson G. On the Treatment of Inoperable Cases of Carcinoma of the Mamma: Suggestions for a New Method of Treatment, with Illustrative Cases.1. The Lancet. 1896; 148(3802): 104-7[DOI]
  • 4. Li CI, Daling JR, Malone KE. Incidence of invasive breast cancer by hormone receptor status from 1992 to 1998. J Clin Oncol. 2003; 21(1): 28-34[PubMed]
  • 5. Hess KR, Pusztai L, Buzdar AU, Hortobagyi GN. Estrogen receptors and distinct patterns of breast cancer relapse. Breast Cancer Res Treat. 2003; 78(1): 105-18[PubMed]
  • 6. Eroles P, Bosch A, Perez-Fidalgo JA, Lluch A. Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. Cancer Treat Rev. 2012; 38(6): 698-707[DOI][PubMed]
  • 7. Johnston SR. New strategies in estrogen receptor-positive breast cancer. Clin Cancer Res. 2010; 16(7): 1979-87[DOI][PubMed]
  • 8. Brewster AM, Hortobagyi GN, Broglio KR, Kau SW, Santa-Maria CA, Arun B, et al. Residual risk of breast cancer recurrence 5 years after adjuvant therapy. J Natl Cancer Inst. 2008; 100(16): 1179-83[DOI][PubMed]
  • 9. Osborne CK, Schiff R. Estrogen-receptor biology: continuing progress and therapeutic implications. J Clin Oncol. 2005; 23(8): 1616-22[DOI][PubMed]
  • 10. Nagaraj G, Ma C. Revisiting the estrogen receptor pathway and its role in endocrine therapy for postmenopausal women with estrogen receptor-positive metastatic breast cancer. Breast Cancer Res Treat. 2015; 150(2): 231-42[DOI][PubMed]
  • 11. Tabarestani S, Ghaderian SM, Rezvani H, Mirfakhraie R, Ebrahimi A, Attarian H, et al. Prognostic and predictive value of copy number alterations in invasive breast cancer as determined by multiplex ligation-dependent probe amplification. Cell Oncol (Dordr). 2014; 37(2): 107-18[DOI][PubMed]
  • 12. Tabarestani S, Ghaderian SM, Rezvani H, Mirfakhraie R. Expression profiling of breast cancer patients treated with tamoxifen: prognostic or predictive significance. Med Oncol. 2014; 31(4): 896[DOI][PubMed]
  • 13. Thomas C, Gustafsson JA. Estrogen receptor mutations and functional consequences for breast cancer. Trends Endocrinol Metab. 2015; 26(9): 467-76[DOI][PubMed]
  • 14. Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, et al. Estrogen receptors: how do they signal and what are their targets. Physiol Rev. 2007; 87(3): 905-31[DOI][PubMed]
  • 15. Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013; 45(12): 1446-51[DOI][PubMed]
  • 16. Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013; 45(12): 1439-45[DOI][PubMed]
  • 17. Niu J, Andres G, Kramer K, Kundranda MN, Alvarez RH, Klimant E, et al. Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients. Onco Targets Ther. 2015; 8: 3323-8[DOI][PubMed]
  • 18. Zhang QX, Borg A, Wolf DM, Oesterreich S, Fuqua SA. An estrogen receptor mutant with strong hormone-independent activity from a metastatic breast cancer. Cancer Res. 1997; 57(7): 1244-9[PubMed]
  • 19. Cancer Genome Atlas N. Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490(7418): 61-70[DOI][PubMed]
  • 20. Butler TM, Johnson-Camacho K, Peto M, Wang NJ, Macey TA, Korkola JE, et al. Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease. PLoS One. 2015; 10(8)[DOI][PubMed]
  • 21. Merenbakh-Lamin K, Ben-Baruch N, Yeheskel A, Dvir A, Soussan-Gutman L, Jeselsohn R, et al. D538G mutation in estrogen receptor-alpha: A novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res. 2013; 73(23): 6856-64[DOI][PubMed]
  • 22. Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, et al. Emergence of constitutively active estrogen receptor-alpha mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res. 2014; 20(7): 1757-67[DOI][PubMed]
  • 23. Sefrioui D, Perdrix A, Sarafan-Vasseur N, Dolfus C, Dujon A, Picquenot JM, et al. Short report: Monitoring ESR1 mutations by circulating tumor DNA in aromatase inhibitor resistant metastatic breast cancer. Int J Cancer. 2015; 137(10): 2513-9[DOI][PubMed]
  • 24. Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, Inao T, Sueta A, Fujiwara S, et al. Droplet digital polymerase chain reaction assay for screening of ESR1 mutations in 325 breast cancer specimens. Transl Res. 2015; 166(6): 540-553 e2[DOI][PubMed]
  • 25. Wang P, Bahreini A, Gyanchandani R, Lucas PC, Hartmaier RJ, Watters RJ, et al. Sensitive Detection of Mono- and Polyclonal ESR1 Mutations in Primary Tumors, Metastatic Lesions, and Cell-Free DNA of Breast Cancer Patients. Clin Cancer Res. 2016; 22(5): 1130-7[DOI][PubMed]
  • 26. Schiavon G, Hrebien S, Garcia-Murillas I, Cutts RJ, Pearson A, Tarazona N, et al. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med. 2015; 7(313): 313ra182[DOI][PubMed]
  • 27. Guttery DS, Page K, Hills A, Woodley L, Marchese SD, Rghebi B, et al. Noninvasive detection of activating estrogen receptor 1 (ESR1) mutations in estrogen receptor-positive metastatic breast cancer. Clin Chem. 2015; 61(7): 974-82[DOI][PubMed]
  • 28. Jeselsohn R, editor Emergence of constitutively active estrogen receptor mutations in advanced estrogen receptor positive breast cancer. 36th San Anonio Breast Cancer Symposium. 2013;
  • 29. Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, et al. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2010; 28(30): 4594-600[DOI][PubMed]
  • 30. Skapek SX, Anderson JR, Hill DA, Henry D, Spunt SL, Meyer W, et al. Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: results of a Children's Oncology Group (COG) phase II study. Pediatr Blood Cancer. 2013; 60(7): 1108-12[DOI][PubMed]
  • 31. McClay EF, McClay MT, Monroe L, Jones JA, Winski PJ. A phase II study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma. Melanoma Res. 2001; 11(3): 309-13[PubMed]
  • 32. Pinkerton JV, Thomas S. Use of SERMs for treatment in postmenopausal women. J Steroid Biochem Mol Biol. 2014; 142: 142-54[DOI][PubMed]
  • 33. Mayer IA, Bardia A, Dickler MN, Mannin HC. Phase I study of ARN-810, a novel selective estrogen receptor degrader, in postmenopausal women with locally advanced or metastatic estrogen receptor positive breast cancer. 2013;
  • 34. Wang Y, Lonard DM, Yu Y, Chow DC, Palzkill TG, Wang J, et al. Bufalin is a potent small-molecule inhibitor of the steroid receptor coactivators SRC-3 and SRC-1. Cancer Res. 2014; 74(5): 1506-17[DOI][PubMed]
  • 35. Yan F, Yu Y, Chow DC, Palzkill T, Madoux F, Hodder P, et al. Identification of verrucarin a as a potent and selective steroid receptor coactivator-3 small molecule inhibitor. PLoS One. 2014; 9(4)[DOI][PubMed]
  • 36. Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009; 11(5)[DOI][PubMed]
  • 37. Albertson DG. Gene amplification in cancer. Trends Genet. 2006; 22(8): 447-55[DOI][PubMed]
  • 38. Holst F, Stahl PR, Ruiz C, Hellwinkel O, Jehan Z, Wendland M, et al. Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nat Genet. 2007; 39(5): 655-60[DOI][PubMed]
  • 39. Adelaide J, Finetti P, Charafe-Jauffret E, Wicinski J, Jacquemier J, Sotiriou C, et al. Absence of ESR1 amplification in a series of breast cancers. Int J Cancer. 2008; 123(12): 2970-2[DOI][PubMed]
  • 40. Tomita S, Zhang Z, Nakano M, Ibusuki M, Kawazoe T, Yamamoto Y, et al. Estrogen receptor alpha gene ESR1 amplification may predict endocrine therapy responsiveness in breast cancer patients. Cancer Sci. 2009; 100(6): 1012-7[DOI][PubMed]
  • 41. Moelans CB, Monsuur HN, de Pinth JH, Radersma RD, de Weger RA, van Diest PJ. ESR1 amplification is rare in breast cancer and is associated with high grade and high proliferation: a multiplex ligation-dependent probe amplification study. Cell Oncol (Dordr). 2011; 34(5): 489-94[DOI][PubMed]
  • 42. Tabarestani S, Ghaderian SM, Rezvani H. Detection of Gene Amplification by Multiplex Ligation-Dependent Probe Amplification in Comparison with In Situ Hybridization and Immunohistochemistry. Asian Pac J Cancer Prev. 2015; 16(17): 7997-8002[PubMed]
  • 43. Ooi A, Inokuchi M, Harada S, Inazawa J, Tajiri R, Kitamura SS, et al. Gene amplification of ESR1 in breast cancers--fact or fiction? A fluorescence in situ hybridization and multiplex ligation-dependent probe amplification study. J Pathol. 2012; 227(1): 8-16[DOI][PubMed]
  • 44. Moelans CB, Holst F, Hellwinkel O, Simon R, van Diest PJ. ESR1 amplification in breast cancer by optimized RNase FISH: frequent but low-level and heterogeneous. PLoS One. 2013; 8(12)[DOI][PubMed]
  • 45. Chen JR, Hsieh TY, Chen HY, Yeh KY, Chen KS, ChangChien YC, et al. Absence of estrogen receptor alpha (ESR1) gene amplification in a series of breast cancers in Taiwan. Virchows Arch. 2014; 464(6): 689-99[DOI][PubMed]
  • 46. Iggo RD, Wood HM, Rabbitts P, Quenel-Tueux N, Mauriac L, MacGrogan G, et al. Abstract PD3-3: Next generation sequencing shows clonal selection after treatment with anastrozole or fulvestrant in a randomized trial of postmenopausal patients with large operable or locally-advanced hormone-receptor-positive breast cancer. Cancer Research. 2014; 73(24 Supplement)[DOI]
Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments