The Role of ESR1 Gene Polymorphic Markers in the Development of Breast Cancer and Resistance to Tamoxifen Therapy

We studied the effect of functionally significant polymorphic markers of the ESR1 gene on the risk of breast cancer, tamoxifen resistance, and survival of patients with this type of cancer. The study included 239 primary breast cancer patients without distant metastases. The analysis of genotype frequency distribution for the studied ESR1 gene polymorphic markers showed the association of the rs2228480 and rs2234693 markers with tamoxifen resistance in the group of patients with luminal B type breast cancer. An association of these two polymorphic markers with the risk of tumor development was also revealed; for rs2234693 polymorphic marker, a relationship with the survival of patients was also showed.

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  1. 1.

    Dronova TA, Babyshkina NN, Zavyalova MV, Patalyak SV, Slonimskaya EM, Cherdyntseva NV, Kzhyshkowska JG. Relation of EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer. Uspekhi Mol. Onkol. 2018;5(3):40-50. Russian.

    Article  Google Scholar 

  2. 2.

    Zavarykina TM, Tyulyandina AS, Loginov VI, Burdennyy AM, Atkarskaya MV, Brenner PK, Kapralova MA, Stenina MB. Association of polymorphic markers of XRCC1, ERCC2, CDKN1A genes with progression free survival of ovarian cancer patients after platinum/taxanes-based chemotherapy. Patognez. 2019;17(1):72-81. Russian.

    Google Scholar 

  3. 3.

    Slonimskaya EM, Vtorushin SV, Babyshkina NN, Patalyak SV. Role of morphological and genetic structural characteristics of estrogen receptor alpha in the development of resistance to endocrinotherapy with tamoxifen in patients with luminal breast cancer. Sib. Onkol. Zh. 2014;(3):39-44. Russian.

    Google Scholar 

  4. 4.

    Anghel A, Raica M, Narita D, Seclaman E, Nicola T, Ursoniu S, Anghel M, Popovici E. Estrogen receptor alpha polymorphisms: correlation with clinicopathological parameters in breast cancer. Neoplasma. 2010;57(4):306-315.

    CAS  Article  Google Scholar 

  5. 5.

    Babyshkina N, Vtorushin S, Dronova T, Patalyak S, Slonimskaya E, Kzhyshkowska J, Cherdyntseva N, Choynzonov E. Impact of estrogen receptor α on the tamoxifen response and prognosis in luminal-A-like and luminal-B-like breast cancer. Clin. Exp. Med. 2019;19(4):547-556.

    Article  Google Scholar 

  6. 6.

    Burstein HJ, Lacchetti C, Anderson H, Buchholz TA, Davidson NE, Gelmon KE, Giordano SH, Hudis CA, Solky AJ, Stearns V, Winer EP, Griggs JJ. Adjuvant Endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on ovarian suppression. J. Clin. Oncol. 2016;34(14):1689-1701.

    CAS  Article  Google Scholar 

  7. 7.

    Chattopadhyay S, Siddiqui S, Akhtar MS, Najm MZ, Deo SV, Shukla NK, Husain SA. Genetic polymorphisms of ESR1, ESR2, CYP17A1, and CYP19A1 and the risk of breast cancer: a case control study from North India. Tumour Biol. 2014;35(5):4517-4527.

    CAS  Article  Google Scholar 

  8. 8.

    Crew KD, Albain KS, Hershman DL, Unger JM, Lo SS. How do we increase uptake of tamoxifen and other anti-estrogens for breast cancer prevention? NPJ Breast Cancer. 2017;3:20.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Higgins MJ, Stearns V. Understanding resistance to tamoxifen in hormone receptor-positive breast cancer. Clin. Chem. 2009;55(8):1453-1455.

    CAS  Article  Google Scholar 

  10. 10.

    Higuchi T, Gohno T, Nagatomo T, Tokiniwa H, Niwa T, Horiguchi J, Oyama T, Takeyoshi I, Hayashi S. Variation in use of estrogen receptor-α gene promoters in breast cancer compared by quantification of promoter-specific messenger RNA. Clin. Breast Cancer. 2014;14(4):249-257.

    CAS  Article  Google Scholar 

  11. 11.

    Hu X, Jiang L, Tang C, Ju Y, Jiu L, Wei Y, Guo L, Zhao Y. Association of three single nucleotide polymorphisms of ESR-1with breast cancer susceptibility: a meta-analysis. J. Biomed. Res. 2017;31(3):213-225.

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Nagini S. Breast cancer: current molecular therapeutic targets and new players. Anticancer Agents Med. Chem. 2017;17(2):152-163.

    CAS  Article  Google Scholar 

  13. 13.

    Sun H, Deng Q, Pan Y, He B, Ying H, Chen J, Liu X, Wang S. Association between estrogen receptor 1 (ESR1) genetic variations and cancer risk: a meta-analysis. J. BUON. 2015; 20(1):296-308.

    CAS  PubMed  Google Scholar 

  14. 14.

    Testa U, Castelli G, Pelosi E. Breast cancer: a molecularly heterogenous disease needing subtype-specific treatments. Med. Sci. (Basel). 2020;8(1).

  15. 15.

    Valdora F, Houssami N, Rossi F, Calabrese M, Tagliafico AS. Rapid review: radiomics and breast cancer. Breast Cancer Res. Treat. 2018;169(2):217-229.

    Article  Google Scholar 

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Correspondence to A. M. Burdennyy.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 9, pp. 345-351, September, 2020

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Lukina, S.S., Burdennyy, A.M., Zavarykina, T.M. et al. The Role of ESR1 Gene Polymorphic Markers in the Development of Breast Cancer and Resistance to Tamoxifen Therapy. Bull Exp Biol Med 170, 350–355 (2021).

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Key Words

  • breast cancer
  • ESR1 gene
  • tamoxifen
  • developmental risk
  • survival