Epigenetic modifications are inherited differences in cellular phenotypes, such as cell gene expression alterations, that occur during somatic cell divisions (also, in rare circumstances, in germ line transmission), but no alterations to the DNA sequence are involved. Histone alterations, polycomb/trithorax associated proteins, short non-coding or short RNAs, long non-coding RNAs (lncRNAs), & DNA methylation are just a few biological processes involved in epigenetic events. These various modifications are intricately linked. The transcriptional potential of genes is closely conditioned by epigenetic control, which is crucial in normal growth and development. Epigenetic mechanisms transmit genomic adaptation to an environment, resulting in a specific phenotype. The purpose of this systematic review is to glance at the roles of Estrogen signalling, polycomb/trithorax associated proteins, DNA methylation in breast cancer progression, as well as epigenetic mechanisms in breast cancer therapy, with an emphasis on functionality, regulatory factors, therapeutic value, and future challenges.

Center of Research for Development Parul University Vadodara Gujarat

Department of Animal Morphology Physiology and Genetics Faculty of AgriSciences Mendel University in Brno Brno Czechia

Department of Applied Physics School of Science Aalto University Espoo Finland

Department of Biotechnology Engineering and Food Technology Chandigarh University Mohali India

Department of Biotechnology School of Applied and Life Sciences Uttaranchal University Dehradun India

Department of Biotechnology School of Engineering and Technology Sharda University Greater Noida India

Department of Civil Engineering Netaji Subhas University of Technology Delhi India

Department of Civil Engineering Rajkiya Engineering College Banda India

Department of Life Science and Bioinformatics Assam University Silchar India

Department of Medical Laboratory Sciences College of Applied Medical Sciences Majmaah University Al Majma'ah Saudi Arabia

Dr A P J Abdul Kalam Technical University Lucknow India

Health and Basic Sciences Research Center Majmaah University Al Majma'ah Saudi Arabia

Small Animal Clinic University of Veterinary Sciences Brno Brno Czechia

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Arpino G., Wiechmann L., Osborne C. K., Schiff R. (2008). Crosstalk between the estrogen receptor and theHER tyrosine kinase receptor family: Molecular mechanism and clinical implications for endocrine therapy resistance. Endocr. Rev. 29, 217–233. 10.1210/er.2006-0045 PubMed DOI PMC

Arun G., Spector D. L. (2019). MALAT1 long non-coding RNA and breast cancer. RNA Biol. 16, 860–863. 10.1080/15476286.2019.1592072 PubMed DOI PMC

Bachman K. E., Rountree M. R., Baylin S. B. (2001). Dnmt3a and Dnmt3b are transcriptional repressors that exhibit unique localization properties to heterochromatin. J. Biol. Chem. 276, 32282–32287. 10.1074/jbc.m104661200 PubMed DOI

Baylin S. B., Ohm J. E. (2006). Epigenetic gene silencing in cancer-mechanism for early oncogenic pathway addiction? Nat. Rev. Cancer 6, 107–116. 10.1038/nrc1799 PubMed DOI

Beatson G. T. (1896). On the treatment of inoperable cases of carcinoma of the mamma: Suggestions for a new method of treatment, with illustrative cases. Trans. Med. Chir. Soc. Edinb. 15, 153–179. PubMed PMC

Bell C. C., Fennell K. A., Chan Y. C., Rambow F., Yeung M. M., Vassiliadis D., et al. (2019). Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia. Nat. Commun. 10, 2723. 10.1038/s41467-019-10652-9 PubMed DOI PMC

Berteaux N., Lottin S., Monte D., Pinte S., Quatannens B., Coll J., et al. (2005). H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. J. Biol. Chem. 280 (33), 29625–29636. 10.1074/jbc.M504033200 PubMed DOI

Bin X., Hongjian Y., Xiping Z., Bo C., Shifeng Y., Binbin T. (2018). Research progresses in roles of LncRNA and its relationships with breast cancer. Cancer Cell. Int. 18, 179. 10.1186/s12935-018-0674-0 PubMed DOI PMC

Bird A. (2002). DNA methylation patterns and epigenetic memory. Genes. Dev. 16, 6–21. 10.1101/gad.947102 PubMed DOI

Bitler B. G., Aird K. M., Garipov A., Li H., Amatangelo M., Kossenkov A. V., et al. (2015). Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers. Nat. Med. 21, 231–238. 10.1038/nm.3799 PubMed DOI PMC

Bolden J. E., Peart M. J., Johnstone R. W. (2006). Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 5, 769–784. 10.1038/nrd2133 PubMed DOI

Bray F., McCarron P., Parkin D. M. (2004). The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res. 6, 229–239. 10.1186/bcr932 PubMed DOI PMC

Brinkman A., de Jong D., Tuinman S., Azaouagh N., van Agthoven T., Dorssers L. C. J. (2010). The substrate domain of BCAR1 is essential for antiestrogen-resistant proliferation of human breast cancer cells. Breast Cancer Res. Treat. 120, 401–408. 10.1007/s10549-009-0403-4 PubMed DOI

Butt A. J., McNeil C. M., Musgrove E. A., Sutherland R. L. (2005). Downstream targets of growth factor and oestrogen signaling and endocrine resistance. Endocrine-Related Cancer. 12, S47–S59. 10.1677/erc.1.00993 PubMed DOI

Chakraborty A. K., Welsh A., Digiovanna M. P. (2010). Co-targeting the insulin-like growth factor I receptor enhances growth-inhibitory and proapoptotic effects of antiestrogens in human breast cancer cell lines. Breast Cancer Res. Treat. 120, 327–335. 10.1007/s10549-009-0382-5 PubMed DOI

Chen S., Wang Y., Zhang J. H., Xia Q. J., Sun Q., Li Z. K., et al. (2017). Long non-coding RNA PTENP1 inhibits proliferation and migration of breast cancer cells via AKT and MAPK signaling pathways. Oncol. Lett. 14 (4), 4659–4662. 10.3892/ol.2017.6823 PubMed DOI PMC

Chen W., Zheng R., Baade P. D., Zhang S., Zeng H., Bray F., et al. (2016). Cancer statistics in China, 2015. CA A Cancer J. Clin. 66, 115–132. 10.3322/caac.21338 PubMed DOI

de Ruijter T. C., van der Heide F., Smits K. M., Aarts M. J., van Engeland M., Heijnen V. C. G. (2020). Prognostic DNA methylation markers for hormone receptor breast cancer: A systematic review. Breast Cancer Res. 22, 13. 10.1186/s13058-020-1250-9 PubMed DOI PMC

De Smet C., Loriot A., Boon T. (2004). Promoter-dependent mechanism leading to selective hypomethylation within the 5′ region of gene MAGE-A1 in tumor cells. Mol. Cell. Biol. 24, 4781–4790. 10.1128/MCB.24.11.4781-4790.2004 PubMed DOI PMC

Derrien T., Johnson R., Bussotti G., Tanzer A., Djebali S., Tilgner H., et al. (2012). The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Res. 22, 1775–1789. 10.1101/gr.132159.111 PubMed DOI PMC

Djebali S., Lagarde J., Kapranov P., Lacroix V., Borel C., Mudge J. M., et al. (2012). Evidence for transcript networks composed of chimeric RNAs in human cells. PLoS One 7, e28213. 10.1371/journal.pone.0028213 PubMed DOI PMC

Early Breast Cancer Trialists’ Collaborative Group (2005). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15- year survival: Overview of the randomised trials. Lancet 365, 1687–1717. PubMed

Encarnacion C. A., Ciocca D. R., McGuire W. L., Clark G. M., Fuqua S. A., Osborne C. K. (1993). Measurement of steroid hormone receptors in breast cancer patients on tamoxifen. Breast Cancer Res. Treat. 26, 237–246. 10.1007/BF00665801 PubMed DOI

Esteller M., Silva J. M., Dominguez G., Bonilla F., Matias-Guiu X., Lerma E., et al. (2000). Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J. Natl. Cancer Inst. 92, 564–569. 10.1093/jnci/92.7.564 PubMed DOI

Evron E., Umbricht C. B., Korz D., Raman V., Loeb D. M., Niranjan B., et al. (2001). Loss of cyclin D2 expression in the majority of breast cancers is associated with promoter hypermethylation. Cancer Res. 61 (6), 2782–2787. 1 TUMOR BIOLOGY| MARCH 01 2001.; PubMed

Fanning S. W., Mayne C. G., Dharmarajan V., Carlson K. E., Martin T. A., Novick S. J., et al. (2016). Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation. Elife 5, e12792. 10.7554/eLife.12792 PubMed DOI PMC

Folgiero V., Avetrani P., Bon G., Di Carlo S. E., Fabi A., Nistico C., et al. (2008). Induction of ErbB-3 expression by alpha6beta4 integrin contributes to tamoxifen resistance in ERbeta1-negative breast carcinomas. PLoS One 3, e1592. 10.1371/journal.pone.0001592 PubMed DOI PMC

Forsberg E. C., Bresnick E. H. (2001). Histone acetylation beyond promoters: Long-range acetylation patterns in the chromatin world. Bioessays. 23, 820–830. 10.1002/bies.1117 PubMed DOI

Fribbens C., O'Leary B., Kilburn L., Hrebien S., Garcia-Murillas I., Beaney M., et al. (2016). Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J. Clin. Oncol. 34, 2961–2968. 10.1200/JCO.2016.67.3061 PubMed DOI

Frigola J., Song J., Stirzaker C., Hinshelwood R. A., Peinado M. A., Clark S. J. (2006). Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band. Nat. Genet. 38, 540–549. 10.1038/ng1781 PubMed DOI

Fukumoto T., Park P. H., Wu S., Fatkhutdinov N., Karakashev S., Nacarelli T., et al. (2018). Repurposing Pan-HDAC inhibitors for ARID1A-mutated ovarian cancer. Cell. Rep. 22, 3393–3400. 10.1016/j.celrep.2018.03.019 PubMed DOI PMC

Gates L. A., Gu G., Chen Y., Rohira A. D., Lei J. T., Hamilton R. A., et al. (2018). Proteomic profiling identifies key coactivators utilized by mutant ERα proteins as potential new therapeutic targets. Oncogene 37, 4581–4598. 10.1038/s41388-018-0284-2 PubMed DOI PMC

Generali D., Berruti A., Brizzi M. P., Campo L., Bonardi S., Wigfield S., et al. (2006). Hypoxia-inducible factor-1alpha expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer. Clin. Cancer Res. 12, 4562–4568. 10.1158/1078-0432.CCR-05-2690 PubMed DOI

Gupta G. P., Massague J. (2006). Cancer metastasis: Building a framework. Cell. 127, 679–695. 10.1016/j.cell.2006.11.001 PubMed DOI

Gutierrez M. C., Detre S., Johnston S., Mohsin S. K., Shou J., Allred D. C., et al. (2005). Molecular changes in tamoxifen-resistant breast cancer:relationship between estrogen receptor, HER-2, and p38 mitogen-activated protein kinase. J. Clin. Oncol. 23, 2469–2476. 10.1200/JCO.2005.01.172 PubMed DOI

Hanahan D., Weinberg R. A. (2011). Hallmarks of cancer: The next generation. Cell. 144, 646–674. 10.1016/j.cell.2011.02.013 PubMed DOI

Hanker A. B., Sudhan D. R., Arteaga C. L. (2020). Overcoming endocrine resistance in breast cancer. Cancer Cell. 37, 496–513. 10.1016/j.ccell.2020.03.009 PubMed DOI PMC

Harrod A., Fulton J., Nguyen V. T. M., Periyasamy M., Ramos-Garcia L., Lai C. F., et al. (2017). Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer. Oncogene 36, 2286–2296. 10.1038/onc.2016.382 PubMed DOI PMC

Helleman J., JansenMP, Ruigrok-Ritstier K., van Staveren I. L., Look M. P., Meijer-van Gelder M. E., et al. (2008). Association of an extracellular matrix gene cluster with breast cancer prognosis and endocrine therapy response. Clin. Cancer Res. 14, 5555–5564. 10.1158/1078-0432.CCR-08-0555 PubMed DOI

Hinshelwood R. A., Clark S. J. (2008). Breast cancer epigenetics: Normal human mammary epithelial cells as a model system. J. Mol. Med. 86, 1315–1328. 10.1007/s00109-008-0386-3 PubMed DOI

Hu Q., Yin J., Zeng A., Jin X., Zhang Z., Yan W., et al. (2018). H19 functions as a competing endogenous RNA to regulate EMT by sponging miR-130a-3p in glioma. Cell. Physiol. biochem. 50 (1), 233–245. 10.1159/000494002 PubMed DOI

Hui R., Macmillan R. D., Kenny F. S., Musgrove E. A., Blamey R. W., Nicholson R. I., et al. (2000). INK4a gene expression and methylation in primary breast cancer: Overexpression of p16INK4a messenger RNA is a marker of poor prognosis. Clin. Cancer Res. 6 (7), 2777–2787. PubMed

Ito K., Barnes P. J., Adcock I. M. (2002). Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin- 1beta-induced histone H4 acetylation on lysines 8 and 12. Mol. Cell. Biol. 20, 6891–6903. 10.1128/MCB.20.18.6891-6903.2000 PubMed DOI PMC

Jadaliha M., Zong X., Malakar P., Ray T., Singh D. K., Freier S. M., et al. (2016). Functional and prognostic significance of long non-coding RNA MALAT1 as a metastasis driver in ER negative lymph node negative breast cancer. Oncotarget 7, 40418–40436. 10.18632/oncotarget.9622 PubMed DOI PMC

Jansen M. P., Foekens J. A., van Staveren I. L., Dirkzwager-Kiel M. M., Ritstier K., Look M. P., et al. (2005). Molecular classification of tamoxifen-resistant breast carcinomas by gene expression profiling. J. Clin. Oncol. 23, 732–740. 10.1200/JCO.2005.05.145 PubMed DOI

Jeselsohn R., Bergholz J. S., Pun M., Cornwell M., Liu W., Nardone A., et al. (2018). Allele-specific chromatin recruitment and therapeutic vulnerabilities of ESR1 activating mutations. Cancer Cell. 33, 173–186.e5. 10.1016/j.ccell.2018.01.004 PubMed DOI PMC

Jeselsohn R., Buchwalter G., De Angelis C., Brown M., Schiff R. (2015). ESR1 mutations—A mechanism for acquired endocrine resistance in breast cancer. Nat. Rev. Clin. Oncol. 12, 573–583. 10.1038/nrclinonc.2015.117 PubMed DOI PMC

Johnson A. B., O’Malley B. W. (2012). Steroid receptor coactivators 1, 2, and 3: Critical regulators of nuclear receptor activity and steroid receptor modulator (SRM)-based cancer therapy. Mol. Cell. Endocrinol. 348, 430–439. 10.1016/j.mce.2011.04.021 PubMed DOI PMC

Jones S., Zhang X., Parsons D. W., Lin J. C., Leary R. J., Angenendt P., et al. (2008). Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801–1806. 10.1126/science.1164368 PubMed DOI PMC

Kanwal R., Pandey M., Natarajan B., MacLennan G. T., Fu P., Lee E Ponsky M. D., et al. (2014). Protection against oxidative DNA damage and stress in human prostate by glutathione S-transferase P1. Mol. Carcinog. 53 (1), 8–18. 10.1002/mc.21939 PubMed DOI PMC

Kern F. G., McLeskey S. W., Zhang L., Kurebayashi J., Liu Y., Ding I. Y., et al. (1994). Transfected MCF-7 cells as a model for breast-cancer progression. Breast Cancer Res. Treat. 31, 153–165. 10.1007/BF00666149 PubMed DOI

Kim T. Y., Bang Y. J., Robertson K. D. (2006). Histone deacetylase inhibitors for cancer therapy. Epigenetics 1, 15–24. 10.4161/epi.1.1.2644 PubMed DOI

Klinge C. M. (2018). Non-coding RNAs in breast cancer: Intracellular and intercellular Communication. Noncoding. RNA 4, 40. 10.3390/ncrna4040040 PubMed DOI PMC

Lavinsky R. M., Jepsen K., Heinzel T., Torchia J., Mullen T. M., Schiff R., et al. (1998). Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes. Proc. Natl. Acad. Sci. U. S. A. 95, 2920–2925. 10.1073/pnas.95.6.2920 PubMed DOI PMC

Levin E. R., Pietras R. J. (2008). Estrogen receptors outside the nucleus in breast cancer. Breast Cancer Res. Treat. 108, 351–361. 10.1007/s10549-007-9618-4 PubMed DOI

Li M., Wang C., Yu B., Zhang X., Shi F., Liu X. (2019). Diagnostic value of RASSF1A methylation for breast cancer: A meta-analysis. Biosci. Rep. 39 (6). 10.1042/bsr20190923 PubMed DOI PMC

Li Z., Xu L., Liu Y., Fu S., Tu J., Hu Y., et al. (2018). LncRNA MALAT1 promotes relapse of breast cancer patients with postoperative fever. Am. J. Transl. Res. 10, 3186–3197. PubMed PMC

Litt M. D., Simpson M., Gaszner M., Allis C. D., Felsenfeld G. (2001). Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus. Science 293, 2453–2455. 10.1126/science.1064413 PubMed DOI

Liu H., Lee E. S., Deb Los Reyes A., Zapf J. W., Jordan V. C. (2001). Silencing and reactivation of the selective estrogen receptor modulator-estrogen receptor alpha complex. Cancer Res. 61, 3632–3639. PubMed

Liu S., Dontu G., Mantle I. D., Patel S., Ahn N. s., Jackson K. W., et al. (2006). Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 66, 6063–6071. 10.1158/0008-5472.CAN-06-0054 PubMed DOI PMC

Liu Y., Du Y., Hu X., Zhao L., Xia W. (2018). Up-regulation of CeRNA TINCR by SP1 contributes to tumorigenesis in breast cancer. BMC Cancer 18, 367. 10.1186/s12885-018-4255-3 PubMed DOI PMC

Lo P. K., Sukumar S. (2008). Epigenomics and breast cancer. Pharmacogenomics 12, 1879–1902. 10.2217/14622416.9.12.1879 PubMed DOI PMC

Lopez-Tarruella S., Schiff R. (2007). The dynamics of estrogen receptor status in breast cancer: Reshaping the paradigm. Clin. Cancer Res. 13, 6921–6925. 10.1158/1078-0432.CCR-07-1399 PubMed DOI

Lu Y., Li T., Wei G., Liu L., Chen Q., Xu L., et al. (2016). The long non-coding RNA NEAT1 regulates epithelial to mesenchymal transition and radioresistance in through MiR-204/ZEB1 Axis in nasopharyngeal carcinoma. Tumour Biol. 37, 11733–11741. 10.1007/s13277-015-4773-4 PubMed DOI

Martin C., Zhang Y. (2005). The diverse functions of histone lysine methylation. Nat. Rev. Mol. Cell. Biol. 6, 838–849. 10.1038/nrm1761 PubMed DOI

Mathur R., Jha A. K. (2020). Reversal of hypermethylation and reactivation of tumor suppressor genes due to natural compounds in breast cancer cells.

Métivier R., Penot G., Hubner M. R., Reid G., Brand H., Kos M., et al. (2003). Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell. 115, 751–763. 10.1016/s0092-8674(03)00934-6 PubMed DOI

Moore M. J., Proudfoot N. J. (2009). Pre-mRNA processing reaches back to transcription and ahead to translation. Cell. 136, 688–700. 10.1016/j.cell.2009.02.001 PubMed DOI

Morel D., Jeffery D., Aspeslagh S., Almouzni G., Postel-Vinay S. (2020). Combining epigenetic drugs with other therapies for solid tumours—Past lessons and future promise. Nat. Rev. Clin. Oncol. 17, 91–107. 10.1038/s41571-019-0267-4 PubMed DOI

Morgan L., Gee J., Pumford S., Farrow L., Finlay P., Robertson J., et al. (2009). Elevated Src kinase activity attenuates tamoxifen response in vitro and is associated with poor prognosis clinically. Cancer Biol. Ther. 8, 1550–1558. 10.4161/cbt.8.16.8954 PubMed DOI

Mukherjee N., Calviello L., Hirsekorn A., de Pretis S., Pelizzola M., Ohler U. (2017). Integrative classification of human coding and noncoding genes through RNA metabolism profiles. Nat. Struct. Mol. Biol. 24, 86–96. 10.1038/nsmb.3325 PubMed DOI

Munzone E., Curigliano G., Rocca A., Bonizzi G., Renne G., Goldhirsch A., et al. (2006). Reverting estrogen-receptor-negative phenotype in HER-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy. Breast Cancer Res. 8, R4. 10.1186/bcr1366 PubMed DOI PMC

Musgrove E. A., Sutherland R. L. (2009). Biological determinants of endocrine resistance in breast cancer. Nat. Rev. Cancer 9, 631–643. 10.1038/nrc2713 PubMed DOI

O’Neil N. J., Bailey M. L., Hieter P. (2017). Synthetic lethality and cancer. Nat. Rev. Genet. 18, 613–623. 10.1038/nrg.2017.47 PubMed DOI

Oronsky B., Oronsky N., Knox S., Fanger G., Scicinski J. (2014). Episensitization: Therapeutic tumor resensitization by epigenetic agents: A review and reassessment. Anticancer. Agents Med. Chem. 14, 1121–1127. 10.2174/1871520614666140418144610 PubMed DOI PMC

Osborne C. K., Bardou V., Hopp T. A., Chamness G. C., Hilsenbeck S. G., Fuqua S. A. W., et al. (2003). Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. J. Natl. Cancer Inst. 95, 353–361. 10.1093/jnci/95.5.353 PubMed DOI

Paakinaho V., Presman D. M., Ball D. A., Johnson T. A., Schiltz R. L., Levitt P., et al. (2017). Single-molecule analysis of steroid receptor and cofactor action in living cells. Nat. Commun. 8, 15896. 10.1038/ncomms15896 PubMed DOI PMC

Peters A. H., Mermoud J. E., Carroll D. O., Pagani M., Schweizer D., Brockdorff N., et al. (2002). Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin. Nat. Genet. 30, 77–80. 10.1038/ng789 PubMed DOI

Pfeifer G. P., Besaratinia A. (2009). Mutational spectra of human cancer. Hum. Genet. 125, 493–506. 10.1007/s00439-009-0657-2 PubMed DOI PMC

Pontiggia O., Rodriguez V., Fabris V., Raffo D., Bumaschny V., Fiszman G., et al. (2009). Establishment of an in vitro estrogen-dependent mouse mammary tumor model: A new tool to understand estrogen responsiveness and development of tamoxifen resistance in the context of stromal-epithelial interactions. Breast Cancer Res. Treat. 116, 247–255. 10.1007/s10549-008-0113-3 PubMed DOI

Ramadan A., Hashim M., Amr Abouzid & Menha Swellam Clinical impact of PTEN methylation status as a prognostic marker for breast cancer J. Genet. Eng. Biotechnol. volume 19, Article number: 66 (2021) PubMed PMC

Razavi P., Chang M. T., Xu G., Bandlamudi C., Ross D. S., Vasan N., et al. (2018). The genomic landscape of endocrine-resistant advanced breast cancers. Cancer Cell. 34, 427–438.e6. 10.1016/j.ccell.2018.08.008 PubMed DOI PMC

Rea S., Eisenhaber F., O’Carroll D., Strahl B. D., Sun Z. W., Schmid M., et al. (2000). Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406, 593–599. 10.1038/35020506 PubMed DOI

Rinn J. L., Chang H. Y. (2012). Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81, 145–166. 10.1146/annurev-biochem-051410-092902 PubMed DOI PMC

Robertson K. D., Ait-Si-Ali S., Yokochi T., Wade P. A., Jones P. L., Wolffe A. P. (2000). DNMT1 forms a complex with Rb, E2F1, and HDAC1 and represses transcription from E2F-responsive promoters. Nat. Genet. 25, 338–342. 10.1038/77124 PubMed DOI

Roth S. Y., Denu J. M., Allis C. D. (2001). Histone acetyltransferases. Annu. Rev. Biochem. 70, 81–120. 10.1146/annurev.biochem.70.1.81 PubMed DOI

Saelee P., Pongtheerat T. (2020). APC promoter hypermethylation as a prognostic marker in breast cancer patients. Asian pac. J. Cancer Prev. 21 (12), 3627–3632. 10.31557/apjcp.2020.21.12.3627 PubMed DOI PMC

Saez-Ayala M., Montenegro M. F., Sanchez-Del-Campo L., Fernandez-Perez M. P., Chazarra S., Freter R., et al. (2013). Directed phenotype switching as an effective antimelanoma strategy. Cancer Cell. 24, 105–119. 10.1016/j.ccr.2013.05.009 PubMed DOI

Santen R. J., Fan P., Zhang Z., Bao Y., Song R. X. D., Yue W. (2009). Estrogen signals via an extranuclear pathway involving IGF-1R and EGFR in tamoxifen-sensitive and -resistant breast cancer cells. Steroids 74, 586–594. 10.1016/j.steroids.2008.11.020 PubMed DOI

Schiff R., Massarweh S. A., Shou J., Bharwani L., Mohsin S. K., Osborne C. K. (2004). Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance. Clin. Cancer Res. 10, 331S–36S. 10.1158/1078-0432.ccr-031212 PubMed DOI

Schubeler D., macAlpine D. M., Scalzo D., Wirbelauer C., Kooperberg C., van Leeuwen F., et al. (2004). The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. Genes. Dev. 518, 1263–1271. 10.1101/gad.1198204 PubMed DOI PMC

Serrano-Gomez S. J., Maziveyi M., Alahari S. K. (2016). Regulation of epithelial mesenchymal transition through epigenetic and post-translational modifications. Mol. Cancer 15, 18. 10.1186/s12943-016-0502-x PubMed DOI PMC

Shang Y., Hu X., DiRenzo J., Lazar M. A., Brown M. (2000). Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell. 103, 843–852. 10.1016/s0092-8674(00)00188-4 PubMed DOI

Shi L., Dong B., Li Z., Lu Y., Ouyang T., Li J., et al. (2009). Expression of ER-{alpha}36, a novel variant of estrogen receptor {alpha}, and resistance to tamoxifen treatment in breast cancer. J. Clin. Oncol. 27, 3423–3429. 10.1200/JCO.2008.17.2254 PubMed DOI PMC

Shiino S., Kinoshita T., Yoshida M., Jimbo K., Asaga S., Takayama S., et al. (2016). Prognostic impact of discordance in hormone receptor status between primary and recurrent sites in patients with recurrent breast cancer. Clin. Breast Cancer 16, e133–e140. 10.1016/j.clbc.2016.05.014 PubMed DOI

Shilatifard A. (2006). Chromatin modifications by methylation and ubiquitination: Implications in the regulation of gene expression. Annu. Rev. Biochem. 75, 243–269. 10.1146/annurev.biochem.75.103004.142422 PubMed DOI

Shin V. Y., Chen J., Cheuk I. W. Y., Siu M. T., Ho C. W., Wang X., et al. (2019). Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness. Cell. Death Dis. 10, 270–310. 10.1038/s41419-019-1513-5 PubMed DOI PMC

Shou J., Massarweh S., Osborne C. K., Wakeling A. E., Ali S., Weiss H., et al. (2004). Mechanisms of tamoxifen resistance: Increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J. Natl. Cancer Inst. 96, 926–935. 10.1093/jnci/djh166 PubMed DOI

Span P. N., Tjan-Heijnen V. C., Manders P., Beex L. V. A. M., Sweep C. G. J. (2003). Cyclin-E is a strong predictor of endocrine therapy failure in human breast cancer. Oncogene 22, 4898–4904. 10.1038/sj.onc.1206818 PubMed DOI

Spoerke J. M., Gendreau S., Walter K., Qiu J., Wilson T. R., Savage H., et al. (2016). Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nat. Commun. 7, 11579. 10.1038/ncomms11579 PubMed DOI PMC

Strahl B. D., Allis C. D. (2000). The language of covalent histone modifications. Nature 403, 41–45. 10.1038/47412 PubMed DOI

Stransky N., Vallot C., Reyal F., Bernard-Pierrot I., de Medina S. G., Segraves R., et al. (2006). Regional copy number-independent deregulation of transcription in cancer. Nat. Genet. 38, 1386–1396. 10.1038/ng1923 PubMed DOI

Suzuki H., Toyota M., Carraway H., Caraway H., Gabrielson E., Ohmura T., et al. (2008). Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer. Br. J. Cancer 98, 1147–1156. 10.1038/sj.bjc.6604259 PubMed DOI PMC

Thomas M. P., Potter B. V. (2013). The structural biology of oestrogen metabolism. J. Steroid Biochem. Mol. Biol. 137, 27–49. 10.1016/j.jsbmb.2012.12.014 PubMed DOI PMC

Tomar D., Yadav A. S., Kumar D., Bhadauriya G., Kundu G. C. (2020). Non-coding RNAs as potential therapeutic targets in breast cancer. Biochim. Biophys. Acta. Gene Regul. Mech. 1863, 194378. 10.1016/j.bbagrm.2019.04.005 PubMed DOI

Turner B. M. (2000). Histone acetylation and an epigenetic code. Bioessays 22, 836–845. 10.1002/1521-1878(200009)22:9<836::aid-bies9>3.0.co;2-x PubMed DOI

Vennin C., Spruyt N., Robin Y. M., Chassat T., Le Bourhis X., Adriaenssens E. (2017). The long non-coding RNA 91 H increases aggressive phenotype of breast cancer cells and up-regulates H19/IGF2 expression through epigenetic modifications. Cancer Lett. 385, 198–206. 10.1016/j.canlet.2016.10.023 PubMed DOI

Wade P. A. (2001). Transcriptional control at regulatory checkpoints by histone deacetylases: Molecular connections between cancer and chromatin. Hum. Mol. Genet. 10, 693–698. 10.1093/hmg/10.7.693 PubMed DOI

Wang M., Han D., Yuan Z., Hu H., Zhao Z., Yang R., et al. (2018). Long non-coding RNA H19 confers 5-Fu resistance in colorectal cancer by promoting SIRT1-mediated autophagy. Cell. Death Dis. 9 (12), 1149. 10.1038/s41419-018-1187-4 PubMed DOI PMC

Wang X., Liu Y., Sun H., Ge A., Li D., Fu J., et al. (2020). DNA methylation in RARβ gene as a mediator of the association between healthy lifestyle and breast cancer: A case-control study. Cancer Manag. Res. 12, 4677–4684. 10.2147/CMAR.S244606 PubMed DOI PMC

Wang Yan, Dan Liangying, Li Qianqian, Li Lili, Lan Zhong, Shao Bianfei, et al. Putti, Xiaoqian He, Yixiao Feng, Yong Lin & Tingxiu Xiang ZMYND10, an epigenetically regulated tumor suppressor, exerts tumor-suppressive functions via miR145-5p/NEDD9 axis in breast cancer Clin. Epigenetics volume 11, Article number: 184 (2019) PubMed PMC

Wils L. J., Bijlsma M. F. (2018). Epigenetic regulation of the Hedgehog and Wnt pathways in cancer. Crit. Rev. Oncol. Hematol. 121, 23–44. 10.1016/j.critrevonc.2017.11.013 PubMed DOI

Wu Jiaxue, Lu Lin-Yu, Yu Xiaochun. (2010). The role of BRCA1 in DNA damage response. Protein Cell. 1 (2), 117–123. 10.1007/s13238-010-0010-5 PubMed DOI PMC

Wu Y., Shao A., Wang L., Hu K., Yu C., Pan C., et al. (2019). The role of LncRNAs in the distant metastasis of breast cancer. Front. Oncol. 9, 407. 10.3389/fonc.2019.00407 PubMed DOI PMC

Xia W., Bacus S., Hegde P., Husain I., Strum J., Liu L., et al. (2006). A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer. Proc. Natl. Acad. Sci. U. S. A. 103, 7795–7800. 10.1073/pnas.0602468103 PubMed DOI PMC

Xiang T., Li L., Yin X., Zhong L., Peng W., Qiu Z., et al. (2013). Epigenetic silencing of the WNT antagonist Dickkopf 3 disrupts normal Wnt/β-catenin signalling and apoptosis regulation in breast cancer cells. J. Cell. Mol. Med. 17, 1236–1246. 10.1111/jcmm.12099 PubMed DOI PMC

Xu D., Bai J., Duan Q., Costa M., Dai W. (2009). Covalent modifications of histones during mitosis and meiosis. Cell. Cycle 8, 3688–3694. 10.4161/cc.8.22.9908 PubMed DOI

Xu G., Chhangawala S., Cocco E., Razavi P., Cai Y., Otto J. E., et al. (2020). ARID1A determines luminal identity and therapeutic response in estrogen-receptor-positive breast cancer. Nat. Genet. 52, 198–207. 10.1038/s41588-019-0554-0 PubMed DOI PMC

Yang S. X., Polley E., Lipkowitz S. (2016). New insights on PI3K/AKT pathway alterations and clinical outcomes in breast cancer. Cancer Treat. Rev. 45, 87–96. 10.1016/j.ctrv.2016.03.004 PubMed DOI PMC

Zardo G., Reale A., De Matteis G., Buontempo S., Caiafa P. (2003). A role for poly (ADP-ribosyl)ation in DNA methylation. Biochem. Cell. Biol. 81, 197–208. 10.1139/o03-050 PubMed DOI

Zhang C. Y., Yu M. S., Li X., Zhang Z., Han C. R., Yan B. (2017). Overexpression of long non-coding RNA MEG3 suppresses breast cancer cell proliferation, invasion, and angiogenesis through AKT pathway. Tumour Biol. 39 (6), 1010428317701311. 10.1177/1010428317701311 PubMed DOI

Zhang Y., Chan H. L., Garcia-Martinez L., Karl D. L., Weich N., Slingerland J. M., et al. (2020). Estrogen induces dynamic ERα and RING1B recruitment to control gene and enhancer activities in luminal breast cancer. Sci. Adv. 6, eaaz7249. 10.1126/sciadv.aaz7249 PubMed DOI PMC

Zhao Z., Chen C., Liu Y., Wu C. (2014). 17β-Estradiol treatment inhibits breast cell proliferation, migration and invasion by decreasing MALAT-1 RNA level. Biochem. Biophys. Res. Commun. 445, 388–393. 10.1016/j.bbrc.2014.02.006 PubMed DOI

Zhou S., He Y., Yang S., Hu J., Zhang Q., Chen W., et al. (2018). The regulatory roles of lncRNAs in the process of breast cancer invasion and metastasis. Biosci. Rep. 38, BSR20180772. 10.1042/BSR20180772 PubMed DOI PMC

Zucchetti B., Shimada A. K., Katz A., Curigliano G. (2019). The role of histone deacetylase inhibitors in metastatic breast cancer. Breast 43, 130–134. 10.1016/j.breast.2018.12.001 PubMed DOI