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Open Access 01-12-2021 | Breast Cancer | Research article

ESR1 PvuII polymorphism: from risk factor to prognostic and predictive factor of the success of primary systemic therapy in advanced breast cancer

Authors: Ramadhan Karsono, Samuel J. Haryono, Bambang Karsono, Wirsma Arif Harahap, Yulia Pratiwi, Teguh Aryandono

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

The ESR1 gene encodes Estrogen Receptor alpha (ERα), which plays a role in the tumourigenesis of breast cancer. A single nucleotide polymorphism (SNP) in intron 1 of this gene called ESR1 PvuII (rs2234693) has been reported to increase the risk of breast cancer. This study aimed to investigate the ESR1 PvuII polymorphism as a prognostic and predictive factor guiding the choice of therapy for advanced breast cancer.

Methods

This retrospective study was conducted in 104 advanced breast cancer patients at Dharmais Cancer Hospital from 2011 to 2018. The ESR1 PvuII polymorphism was analysed by Sanger sequencing of DNA from primary breast tumour samples.

Results

The percentages of patients with ESR1 PvuII genotypes TT, TC, and CC were 42.3, 39.4, and 18.3%, respectively. Looking at prognosis, patients with ESR1 PvuII TC + CC had shorter overall survival than those with the TT genotype [HR = 1.79; 95% CI 1.05–3.04; p = 0.032]. As a predictive marker, TC + CC was associated with shorter survival (p = 0.041), but TC + CC patients on primary hormonal therapy had a median overall survival longer than TC + CC patients on primary chemotherapy (1072 vs 599 days).

Conclusion

The ESR1 PvuII TC + CC genotypes confer poor prognosis in advanced breast cancer, but these genotypes could be regarded as a good predictor of the therapeutic effect of hormonal treatment.

Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn H-J, et al. Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol Off J Eur Soc Med Oncol [Internet]. 2011 Aug [cited 2019 Apr 15];22(8):1736–47. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21709140.

Roychowdhury S, Iyer MK, Robinson DR, Lonigro RJ, Wu Y-M, Cao X, et al. Personalized oncology through integrative high-throughput sequencing: a pilot study. Sci Transl Med 2011;3(111):1–20.

Markiewicz A, Wełnicka-Jaśkiewicz M, Skokowski J, Jaśkiewicz J, Szade J, Jassem J, et al. Prognostic Significance of ESR1 Amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 Polymorphisms in Breast Cancer Patients. Medeiros R, editor. PLoS One [Internet]. 2013 Aug 8 [cited 2019 Apr 16];8(8):e72219. Available from: https://dx.plos.org/10.1371/journal.pone.0072219

Robinson DR, Wu Y-M, 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.CrossRef

Jeselsohn R. Are we ready to use ESR1 mutations in clinical practice? Breast Care [Internet]. 2017;12(5):309–13 Available from: https://www.karger.com/Article/FullText/481428.CrossRef

Reinert T, Saad ED, Barrios CH, Bines J. Clinical implications of eSR1 mutations in hormone receptor-positive advanced breast Cancer. Front Oncol. 2017;7(March):1–9.

Niu J, Andres G, Kramer K, Kundranda M, Alvarez R, Klimant E, et al. Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients. Onco Targets Ther [Internet]. 2015 Nov 11 [cited 2019 Apr 18];8:3323. Available from: https://www.dovepress.com/incidence-and-clinical-significance-of-esr1-mutations-in-heavily-pretr-peer-reviewed-article-OTT

Carson E, Dear R. Advanced breast cancer: An update to systemic therapy. Aust J Gen Pract [Internet]. 2019 May 1 [cited 2020 May 11];48(5):278–83. Available from: https://www1.racgp.org.au/ajgp/2019/may/advanced-breast-cancer-an-update-to-systemic-thera

NCCN. NCCN Clinical Practice Guidelines in Oncology : Breast Cancer. Netw Natl Compr Cancer. 2018;1.

10.

Widodo I, Dwianingsih EK, Triningsih E, Utoro T, Soeripto. Clinicopathological features of Indonesian breast cancers with different molecular subtypes. Asian Pacific J Cancer Prev. 2014;

11.

Akhsan A, Aryandono T. Prognostic factors of locally advanced breast cancer patients receiving neoadjuvant and adjuvant chemotherapy. Asian Pac J Cancer Prev. 2010;11(3):759–761. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21039049.

12.

Wilcken N, Hornbuckle J, Ghersi D. Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer. Cochrane Database Syst Rev. 2003;(2):CD002747. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12804433.

13.

Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, et al. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer. 2007;110(2):244–54.CrossRef

14.

Karsono R, Purwanto DJ, Haryono SJ, Karsono B, Sari L, Pratiwi Y, et al. Preoperative Neoadjuvant hormonal therapy and Neoadjuvant chemotherapy for stage 3B and 4 breast Cancer patients in Dharmais hospital-National Cancer Center, Indonesia: a cohort study. Indones J Cancer. 2019;12(4):109.CrossRef

15.

Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, et al. Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer a systematic review and meta-analysis. JAMA Oncol. 2016;2(11):1477–86.CrossRef

16.

Palmieri C, Cleator S, Kilburn LS, Kim SB, Ahn SH, Beresford M, et al. NEOCENT: a randomized feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer. Breast Cancer Res Treat. 2014;148(3):581–90.CrossRef

17.

Alba E, Calvo L, Albanell J, De la Haba JR, Arcusa Lanza A, Chacon JI, et al. Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study. Ann Oncol. 2012;23(12):3069–74.CrossRef

18.

Saad ED, Katz A, Buyse M. Overall Survival and Post-Progression Survival in Advanced Breast Cancer : A Review of Recent Randomized Clinical Trials. 2018;28(11).

19.

Lu H, Chen D, Hu L-P, Zhou L-L, Xu H-Y, Bai Y-H, et al. Estrogen receptor alpha gene polymorphisms, and breast Cancer risk: a case-control study with Meta-analysis combined. Asian Pacific J Cancer Prev. 2014;14(11):6743–9.CrossRef

20.

Bahreini A, Levine K, Santana-Santos L, Benos P V, Wang P, Andersen C, et al. Non-coding single nucleotide variants affecting estrogen receptor binding and activity. Genome Med [Internet]. 2016 [cited 2020 May 11];8(128):1–11. Available from: http://www.pgrr.pitt.edu/pgrr

21.

Toy W, Weir H, Razavi P, Lawson M, Goeppert AU, Mazzola AM, et al. Activating ESR1 mutations differentially affect the efficacy of ER antagonists. Cancer Discov. 2017;7(3):277–87.CrossRef

22.

Billam M, Witt AE, Davidson NE. The silent estrogen receptor: can we make it speak? Cancer Biol Ther. 2009;8(6):485–96.CrossRef

23.

Hertz DL, Henry NL, Kidwell KM, Thomas D, Goddard A, Azzouz F, et al. ESR1 and PGR polymorphisms are associated with estrogen and progesterone receptor expression in breast tumors. Physiol Genomics. 2016 Sep 1;48(9):688–98.CrossRef

24.

Gown AM. Current issues in ER and HER2 testing by IHC in breast cancer. Mod Pathol. 2008;21:S8–15.CrossRef

25.

Hu X, Jiang L, Tang C, Ju Y, Jiu L, Wei Y, et al. Association of three single nucleotide polymorphisms of ESR1 with breast cancer susceptibility: a meta-analysis. J Biomed Res. 2017;31(3):213–25.PubMedPubMedCentral

26.

Chandarlapaty S, Chen D, He W, Sung P, Samoila A, You D, et al. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast Cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol. 2016;2(10):1310–5.CrossRef

27.

Kuo S, Yang S, You S, Lien H, Lin C-H, Lin P-H, et al. Polymorphisms of ESR1, UGT1A1, HCN1, MAP 3K1, and CYP2B6 are associated with the prognosis of hormone receptor-positive early breast cancer. Oncotarget [Internet]. 2017 Mar 28;8(13):20925–38 Available from: http://www.oncotarget.com/fulltext/14995.CrossRef

28.

Clatot F, Perdrix A, Augusto L, Beaussire L, Delacour J, Calbrix C, et al. Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor. Oncotarget [Internet]. 2016 Nov 15 [cited 2019 May 9];7(46):74448–59. Available from: http://www.oncotarget.com/fulltext/12950

Title: ESR1 PvuII polymorphism: from risk factor to prognostic and predictive factor of the success of primary systemic therapy in advanced breast cancer
Authors: Ramadhan Karsono
Samuel J. Haryono
Bambang Karsono
Wirsma Arif Harahap
Yulia Pratiwi
Teguh Aryandono
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Cytostatic Therapy
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-09083-x

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