DOI QR코드

DOI QR Code

Tamoxifen Resistance in Breast Cancer

  • Chang, Min-Sun (Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women's University)
  • Received : 2012.03.06
  • Accepted : 2012.04.02
  • Published : 2012.05.31

Abstract

Tamoxifen is a central component of the treatment of estrogen receptor (ER)-positive breast cancer as a partial agonist of ER. It has been clinically used for the last 30 years and is currently available as a chemopreventive agent in women with high risk for breast cancer. The most challenging issue with tamoxifen use is the development of resistance in an initially responsive breast tumor. This review summarizes the roles of ER as the therapeutic target of tamoxifen in cancer treatment, clinical values and issues of tamoxifen use, and molecular mechanisms of tamoxifen resistance. Emerging knowledge on the molecular mechanisms of tamoxifen resistance will provide insight into the design of regimens to overcome tamoxifen resistance and discovery of novel therapeutic agents with a decreased chance of developing resistance as well as establishing more efficient treatment strategies.

Keywords

References

  1. Anderson, W. F., Chatterjee, N., Ershler, W. B. and Brawley, O. W. (2002) Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res. Treat. 76, 27-36. https://doi.org/10.1023/A:1020299707510
  2. Angel, P. and Karin, M. (1991) The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim. Biophys. Acta 1072, 129-157.
  3. Anzick, S. L., Kononen, J., Walker, R. L., Azorsa, D. O., Tanner, M. M., Guan, X. Y., Sauter, G., Kallioniemi, O. P., Trent, J. M. and Meltzer, P. S. (1997) AIB1, a steroid receptor coactivator amplifi ed in breast and ovarian cancer. Science 277, 965-968. https://doi.org/10.1126/science.277.5328.965
  4. Arpino, G., Gutierrez, C., Weiss, H., Rimawi, M., Massarweh, S., Bharwani, L., De Placido, S., Osborne, C. K. and Schiff, R. (2007) Treatment of human epidermal growth factor receptor 2-overexpressing breast cancer xenografts with multiagent HER-targeted therapy. J. Natl. Cancer Inst. 99, 694-705. https://doi.org/10.1093/jnci/djk151
  5. Banerjee, S., Saxena, N., Sengupta, K. and Banerjee, S. K. (2003) 17alpha-estradiol-induced VEGF-A expression in rat pituitary tumor cells is mediated through ER independent but PI3K-Akt dependent signaling pathway. Biochem. Biophys. Res. Commun. 300, 209-215. https://doi.org/10.1016/S0006-291X(02)02830-9
  6. Benz, C. C., Scott, G. K., Sarup, J. C., Johnson, R. M., Tripathy, D., Coronado, E., Shepard, H. M. and Osborne, C. K. (1992) Estrogendependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res. Treat. 24, 85-95. https://doi.org/10.1007/BF01961241
  7. Bjornström, L. and Sjöberg, M. (2005) Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol. Endocrinol. 19, 833-842. https://doi.org/10.1210/me.2004-0486
  8. Bocchinfuso, W. P. and Korach, K. S. (1997) Estrogen receptor residues required for stereospecifi c ligand recognition and activation. Mol. Endocrinol. 11, 587-594. https://doi.org/10.1210/me.11.5.587
  9. Bolton, J. L. and Thatcher, G. R. (2008) Potential mechanisms of estrogen quinone carcinogenesis. Chem. Res. Toxicol. 21, 93-101. https://doi.org/10.1021/tx700191p
  10. Borges, S., Desta, Z., Li, L., Skaar, T. C., Ward, B. A., Nguyen, A., Jin, Y., Storniolo, A. M., Nikoloff, D. M., Wu, L., Hillman, G., Hayes, D. F., Stearns, V. and Flockhart, D. A. (2006) Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin. Pharmacol. Ther. 80, 61-74. https://doi.org/10.1016/j.clpt.2006.03.013
  11. Brunner, N., Boysen, B., Jirus, S., Skaar, T. C., Holst-Hansen, C., Lippman, J., Frandsen, T., Spang-Thomsen, M., Fuqua, S. A. and Clarke, R. (1997) MCF7/LCC9: an antiestrogen-resistant MCF-7 variant in which acquired resistance to the steroidal antiestrogen ICI 182,780 confers an early cross-resistance to the nonsteroidal antiestrogen tamoxifen. Cancer Res. 57, 3486-3493.
  12. Brzozowski, A. M., Pike, A. C., Dauter, Z., Hubbard, R. E., Bonn, T., Engström, O., Ohman, L., Greene, G. L., Gustafsson, J. A. and Carlquist, M. (1997) Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389, 753-758. https://doi.org/10.1038/39645
  13. Bursch, W., Ellinger, A., Kienzl, H., Török, L., Pandey, S., Sikorska, M., Walker, R. and Hermann, R. S. (1996) Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy. Carcinogenesis 17, 1595-1607. https://doi.org/10.1093/carcin/17.8.1595
  14. Caraci, F., Crupi, R., Drago, F. and Spina. E. (2011) Metabolic drug interactions between antidepressants and anticancer drugs: focus on selective serotonin reuptake inhibitors and hypericum extract. Curr. Drug Metab. 12, 570-577. https://doi.org/10.2174/138920011795713706
  15. Cavalieri, E., Chakravarti, D., Guttenplan, J., Hart, E., Ingle, J., Jankowiak, R., Muti, P., Rogan, E., Russo, J., Santen, R. and Sutter, T. (2006) Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention. Biochim. Biophys. Acta 1766, 63-78.
  16. Chang, M., Liu, H. and Jordan, V. C. (2002). Hormonal and growth factors. In Cancer of the Breast (P. M. Dansette, R. Snyder, M. Delaforge, G. G. Gibson, H. Greim, D. J. Jollow, T. J. Monks and I. G. Sipes, Eds.), pp. 417-441. Saunders, Philadelphia, USA.
  17. Chang, X. Z., Li, D. Q., Hou, Y. F., Wu, J., Lu, J.S., Di, G. H., Jin, W., Ou, Z. L., Shen, Z. Z. and Shao, Z. M. (2007) Identifi cation of the functional role of peroxiredoxin 6 in the progression of breast cancer. Breast Cancer Res. 9, R76. https://doi.org/10.1186/bcr1789
  18. Clarke, R., Currier, S., Kaplan, O., Lovelace, E., Boulay, V., Gottesman, M. M. and Dickson, R. B. (1992) Effect of P-glycoprotein expression on sensitivity to hormones in MCF-7 human breast cancer cells. J. Natl. Cancer Inst. 84, 1506-1512. https://doi.org/10.1093/jnci/84.19.1506
  19. Clarke, R., Dickson, R. B. and Brünner, N. (1990) The process of malignant progression in human breast cancer. Ann. Oncol. 1, 401-407.
  20. Clarke, R. B., Howell, A., Potten, C. S. and Anderson, E. (1997) Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res. 57, 4987-4991.
  21. Crawford, A. C., Riggins, R. B., Shajahan, A. N., Zwart, A. and Clarke, R. (2010) Co-inhibition of BCL-W and BCL2 restores antiestrogen sensitivity through BECN1 and promotes an autophagy-associated necrosis. PLoS One 5, e8604. https://doi.org/10.1371/journal.pone.0008604
  22. Creighton, C. J., Massarweh, S., Huang, S., Tsimelzon, A., Hilsenbeck, S. G., Osborne, C. K., Shou, J., Malorni, L. and Schiff, R. (2008) Development of resistance to targeted therapies transforms the clinically associated molecular profi le subtype of breast tumor xenografts. Cancer Res. 68, 7493-7501. https://doi.org/10.1158/0008-5472.CAN-08-1404
  23. Crewe, H. K., Notley, L. M., Wunsch, R. M., Lennard, M. S. and Gillam, E. M. (2002) Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab. Dispos. 30, 869-874. https://doi.org/10.1124/dmd.30.8.869
  24. Croker, A. K., Goodale, D., Chu, J., Postenka, C., Hedley, B. D., Hess, D. A. and Allan, A. L. (2009) High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J. Cell Mol. Med. 13, 2236-2252. https://doi.org/10.1111/j.1582-4934.2008.00455.x
  25. Dawson, S. J., Provenzano, E. and Caldas, C. (2009) Triple negative breast cancers: clinical and prognostic implications. Eur. J. Cancer 45 Suppl 1, 27-40. https://doi.org/10.1016/S0959-8049(09)70013-9
  26. Denton, K. M., Shweta, A. and Anderson, W. P. (2002) Preglomerular and postglomerular resistance responses to different levels of sympathetic activation by hypoxia. J. Am. Soc. Nephrol. 13, 27-34.
  27. Dontu, G., El-Ashry, D. and Wicha, M. S. (2004) Breast cancer, stem/ progenitor cells and the estrogen receptor. Trends Endocrinol. Metab. 15, 193-197. https://doi.org/10.1016/j.tem.2004.05.011
  28. Dowsett, M. and Haynes, B. P. (2003) Hormonal effects of aromatase inhibitors: focus on premenopausal effects and interaction with tamoxifen. J. Steroid Biochem. Mol. Biol. 86, 255-263. https://doi.org/10.1016/S0960-0760(03)00365-0
  29. EBCTCG (Early Breast Cancer Trialist' Collaborative Group). (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet 351, 1451-1467. https://doi.org/10.1016/S0140-6736(97)11423-4
  30. EBCTCG (Early Breast Cancer Trialist' Collaborative Group). (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365, 1687-1717. https://doi.org/10.1016/S0140-6736(05)66544-0
  31. Encarnación, C. A., Ciocca, D. R., McGuire, W. L., Clark, G. M., Fuqua, S. A. and Osborne, C. K. (1993) Measurement of steroid hormone receptors in breast cancer patients on tamoxifen. Breast Cancer Res. Treat. 26, 237-246. https://doi.org/10.1007/BF00665801
  32. Fan, P. W. and Boltonm J, L. (2001) Bioactivation of tamoxifen to metabolite E quinone methide: reaction with glutathione and DNA. Drug Metab. Dispos. 29, 891-896.
  33. Forbes, J. F., Cuzick, J., Buzdar, A., Howell, A., Tobias, J. S. and Baum, M; Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group. (2008) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 9, 45-53. https://doi.org/10.1016/S1470-2045(07)70385-6
  34. Fridovich, I. (1999) Fundamental aspects of reactive oxygen species, or what's the matter with oxygen? Ann. N. Y. Acad. Sci. 893, 13-18. https://doi.org/10.1111/j.1749-6632.1999.tb07814.x
  35. Fuqua, S. A. (1994) Estrogen receptor mutagenesis and hormone resistance. Cancer 74 (3 Suppl), 1026-1029. https://doi.org/10.1002/1097-0142(19940801)74:3+<1026::AID-CNCR2820741509>3.0.CO;2-K
  36. Gee, J. M., Harper, M. E., Hutcheson, I. R., Madden, T. A., Barrow, D., Knowlden, J. M., McClelland, R. A., Jordan, N., Wakeling, A. E. and Nicholson, R. I. (2003) The antiepidermal growth factor receptor agent gefi tinib (ZD1839/Iressa) improves antihormone response and prevents development of resistance in breast cancer in vitro. Endocrinology 144, 5105-5117. https://doi.org/10.1210/en.2003-0705
  37. Girault, I., Bièche, I. and Lidereau, R. (2006) Role of estrogen receptor alpha transcriptional coregulators in tamoxifen resistance in breast cancer. Maturitas 54, 342-351. https://doi.org/10.1016/j.maturitas.2006.06.003
  38. Goetz, M. P., Knox, S. K., Suman, V. J., Rae, J. M., Safgren, S. L., Ames, M. M., Visscher, D. W., Reynolds, C., Couch, F. J., Lingle, W.L., Weinshilboum, R. M., Fritcher, E. G., Nibbe, A. M., Desta, Z., Nguyen, A., Flockhart, D. A., Perez, E. A. and Ingle, J. N. (2007) The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res. Treat. 101, 113-121. https://doi.org/10.1007/s10549-006-9428-0
  39. Goetz, M. P., Rae, J. M., Suman, V. J., Safgren, S. L., Ames, M. M., Visscher, D. W., Reynolds, C., Couch, F. J., Lingle, W. L., Flockhart, D. A., Desta, Z., Perez, E. A. and Ingle, J. N. (2005) Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J. Clin. Oncol. 23, 9312-9318. https://doi.org/10.1200/JCO.2005.03.3266
  40. Gonzalez-Angulo, A. M., Morales-Vasquez, F. and Hortobagyi, G. N. (2007) Overview of resistance to systemic therapy in patients with breast cancer. Adv. Exp. Med. Biol. 608, 1-22. https://doi.org/10.1007/978-0-387-74039-3_1
  41. Goss, P. E., Ingle, J. N., Martino, S., Robert, N. J., Muss, H. B., Piccart, M. J., Castiglione, M., Tu, D., Shepherd, L. E., Pritchard, K. I., Livingston, R. B., Davidson, N. E., Norton, L., Perez, E. A., Abrams, J. S., Cameron, D. A., Palmer, M. J. and Pater, J. L.; National Cancer Institute of Canada Clinical Trials Group MA.17. (2007) Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada Clinical Trials Group MA.17. J. Clin. Oncol. 25, 2006-2011. https://doi.org/10.1200/JCO.2006.09.4482
  42. Goss, P. E., Ingle, J. N., Martino, S., Robert, N. J., Muss, H. B., Piccart, M. J., Castiglione, M., Tu, D., Shepherd, L. E., Pritchard, K. I., Livingston, R. B., Davidson, N. E., Norton, L., Perez, E. A., Abrams, J. S., Cameron, D. A., Palmer M. J. and Pater, J. L. (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated fi ndings from NCIC CTG MA.17. J. Natl. Cancer Inst. 97, 1262-1271. https://doi.org/10.1093/jnci/dji250
  43. Gottardis, M. M. and Jordan, V. C. (1988) Development of tamoxifenstimulated growth of MCF-7 tumors in athymic mice after long-term antiestrogen administration. Cancer Res. 48, 5183-5187.
  44. Graham, M. L., 2nd, Smith, J. A., Jewett, P. B. and Horwitz, K. B. (1992) Heterogeneity of progesterone receptor content and remodeling by tamoxifen characterize subpopulations of cultured human breast cancer cells: analysis by quantitative dual parameter flow cytometry. Cancer Res. 52, 593-602.
  45. Greene, G. L., Gilna, P., Waterfi eld, M., Baker, A., Hort, Y. and Shine, J. (1986) Sequence and expression of human estrogen receptor complementary DNA. Science 231, 1150-1154. https://doi.org/10.1126/science.3753802
  46. Habel, L. A. and Stanford, J. L. (1993) Hormone receptors and breast cancer. Epidemiol. Rev. 15, 209-219.
  47. Heldring, N., Pike, A., Andersson, S., Matthews, J., Cheng, G., Hartman, J., Tujague, M., Ström, A., Treuter, E., Warner, M. and Gustafsson, J. A. (2007) Estrogen receptors: how do they signal and what are their targets. Physiol. Rev. 87, 905-931. https://doi.org/10.1152/physrev.00026.2006
  48. Henderson, B. E. and Feigelson, H. S. (2000) Hormonal carcinogenesis. Carcinogenesis 21, 427-433. https://doi.org/10.1093/carcin/21.3.427
  49. Holloway, J. N., Murthy, S. and El-Ashry, D. (2004) A cytoplasmic substrate of mitogen-activated protein kinase is responsible for estrogen receptor-alpha down-regulation in breast cancer cells: the role of nuclear factor-kappaB. Mol. Endocrinol. 18, 1396-1410. https://doi.org/10.1210/me.2004-0048
  50. Howell, A., Robertson, J. F., Quaresma Albano, J., Aschermannova, A., Mauriac, L., Kleeberg, U. R., Vergote, I., Erikstein, B., Webster, A. and Morris, C. (2002) Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J. Clin. Oncol. 20, 3396-3403. https://doi.org/10.1200/JCO.2002.10.057
  51. Hurtubise, A. and Momparler, R. L. (2006) Effect of histone deacetylase inhibitor LAQ824 on antineoplastic action of 5-Aza-2'-deoxycytidine (decitabine) on human breast carcinoma cells. Cancer Chemother. Pharmacol. 58, 618-625. https://doi.org/10.1007/s00280-006-0225-6
  52. Ingle, J. N., Mailliard, J. A., Schaid, D. J., Krook, J. E., Gesme, D. H., Jr, Windschitl, H. E., Pfeifl e, D.M., Etzell, P. S., Gerstner, J. G. and Long, H. J., et al. (1991) A double-blind trial of tamoxifen plus prednisolone versus tamoxifen plus placebo in postmenopausal women with metastatic breast cancer. A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic. Cancer 68, 34-39. https://doi.org/10.1002/1097-0142(19910701)68:1<34::AID-CNCR2820680107>3.0.CO;2-Q
  53. Jaiyesimi, I. A., Buzdar, A. U., Decker, D. A. and Hortobagyi, G. N. (1995) Use of tamoxifen for breast cancer: twenty-eight years later. J. Clin. Oncol. 13, 513-529.
  54. Jemal, A., Siegel, R., Xu, J. and Ward, E. (2010) Cancer statistics, 2010. CA Cancer J. Clin. 60, 277-300. https://doi.org/10.3322/caac.20073
  55. Jiang, S. Y., Langan-Fahey, S. M., Stella, A. L., McCague, R. and Jordan, V. C. (1992) Point mutation of estrogen receptor (ER) in the ligand-binding domain changes the pharmacology of antiestrogens in ER-negative breast cancer cells stably expressing complementary DNAs for ER. Mol. Endocrinol. 6, 2167-2174. https://doi.org/10.1210/me.6.12.2167
  56. Jin, S. (2006) Autophagy, mitochondrial quality control, and oncogenesis. Autophagy 2, 80-84. https://doi.org/10.4161/auto.2.2.2460
  57. Jin, Y., Desta, Z., Stearns, V., Ward, B., Ho, H., Lee, K. H., Skaar, T., Storniolo, A. M., Li, L., Araba, A., Blanchard, R., Nguyen, A., Ullmer, L., Hayden, J., Lemler, S., Weinshilboum, R. M., Rae, J. M., Hayes, D. F. and Flockhart, D. A. (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J. Natl. Cancer Inst. 97, 30-39. https://doi.org/10.1093/jnci/dji005
  58. John, S., Nayvelt, I., Hsu, H. C., Yang, P., Liu, W., Das, G. M., Thomas, T. and Thomas, T. J. (2008) Regulation of estrogenic effects by beclin 1 in breast cancer cells. Cancer Res. 68, 7855-7863. https://doi.org/10.1158/0008-5472.CAN-07-5875
  59. Johnson, M. D., Zuo, H., Lee, K. H., Trebley, J. P., Rae, J. M., Weatherman, R. V., Desta, Z., Flockhart, D. A. and Skaar, T. C. (2004) Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res. Treat. 85, 151-159. https://doi.org/10.1023/B:BREA.0000025406.31193.e8
  60. Johnston, S. R. (2010) New strategies in estrogen receptor-positive breast cancer. Clin. Cancer Res. 16, 1979-1987. https://doi.org/10.1158/1078-0432.CCR-09-1823
  61. Johnston, S. R., Haynes, B. P., Smith, I. E., Jarman, M., Sacks, N. P., Ebbs, S. R. and Dowsett, M. (1993) Acquired tamoxifen resistance in human breast cancer and reduced intra-tumoral drug concentration. Lancet 342, 1521-1522. https://doi.org/10.1016/S0140-6736(05)80088-1
  62. Johnston, S. R., Semiglazov, V. F., Manikhas, G. M., Spaeth, D., Romieu, G., Dodwell, D. J., Wardley, A. M., Neven, P., Bessems, A., Park, Y. C., De Porre, P. M., Perez Ruixo, J. J. and Howes, A. J. (2008) A phase II, randomized, blinded study of the farnesyltransferase inhibitor tipifarnib combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy. Breast Cancer Res. Treat. 110, 327-335. https://doi.org/10.1007/s10549-007-9726-1
  63. Jordan, V. C. (1977) Effects of tamoxifen in relation to breast cancer. Br. Med. J. 1, 1534-1535.
  64. Jordan, V. C. (2004) Selective estrogen receptor modulation: concept and consequences in cancer. Cancer Cell 5, 207-213. https://doi.org/10.1016/S1535-6108(04)00059-5
  65. Jordan, V. C., Collins, M. M., Rowsby, L. and Prestwich, G. (1997) A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J. Endocrinol. 75, 305-316.
  66. Karihtala, P., Mantyniemi, A., Kang, S. W., Kinnula, V. L. and Soini, Y. (2003) Peroxiredoxins in breast carcinoma. Clin. Cancer Res. 15, 3418-3424.
  67. Katzenellenbogen, B. S., Miller, M. A., Mullick, A. and Sheen, Y. Y. (1985) Antiestrogen action in breast cancer cells: modulation of proliferation and protein synthesis, and interaction with estrogen receptors and additional antiestrogen binding sites. Breast Cancer Res. Treat. 5, 231-243. https://doi.org/10.1007/BF01806018
  68. Keeling, J. W., Ozer, E., King, G. and Walker, F. (2000) Oestrogen receptor alpha in female fetal, infant, and child mammary tissue. J. Pathol. 191, 449-451. https://doi.org/10.1002/1096-9896(2000)9999:9999<::AID-PATH661>3.0.CO;2-#
  69. Kim, P. M. and Wells, P. G. (1996) Genoprotection by UDP-glucuronosyltransferases in peroxidase-dependent, reactive oxygen species-mediated micronucleus initiation by the carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene. Cancer Res. 56, 1526-1532.
  70. Klinge, C. M. (2000) Estrogen receptor interaction with co-activators and co-repressors. Steroids 65, 227-251. https://doi.org/10.1016/S0039-128X(99)00107-5
  71. Kryston, T. B., Georgiev, A. B., Pissis, P. and Georgakilas, A. G. (2011) Role of oxidative stress and DNA damage in human carcinogenesis. Mutat. Res. 711, 193-201. https://doi.org/10.1016/j.mrfmmm.2010.12.016
  72. Kuehl, P., Zhang, J., Lin, Y., Lamba, J., Assem, M., Schuetz, J., Watkins, P. B., Daly, A., Wrighton, S. A., Hall, S. D., Maurel, P., Relling, M., Brimer, C., Yasuda, K., Venkataramanan, R., Strom, S., Thummel, K., Boguski, M. S. and Schuetz, E. (2001) Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat. Genet. 27, 383-391. https://doi.org/10.1038/86882
  73. Kuiper, G. G., Carlsson, B., Grandien, K., Enmark, E., Haggblad, J., Nilsson, S. and Gustafsson, J. A. (1997) Comparison of the ligand binding specifi city and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138, 863-870. https://doi.org/10.1210/en.138.3.863
  74. Kurosumi, M. (2003) Signifi cance of immunohistochemical assessment of steroid hormone receptor status for breast cancer patients. Breast Cancer 10, 97-104. https://doi.org/10.1007/BF02967633
  75. Lavinsky, R. M., Jepsen, K., Heinzel, T., Torchia, J., Mullen, T. M., Schiff, R., Del-Rio, A. L., Ricote, M., Ngo, S., Gemsch, J., Hilsenbeck, S. G., Osborne, C. K., Glass, C. K., Rosenfeld, M. G. and Rose, D. W. (1998) Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes. Proc. Natl. Acad. Sci. USA 95, 2920-2925. https://doi.org/10.1073/pnas.95.6.2920
  76. Levenson, A. S., Catherino, W. H. and Jordan, V. C. (1997) Estrogenic activity is increased for an antiestrogen by a natural mutation of the estrogen receptor. J. Steroid. Biochem. Mol. Biol. 60, 261-268. https://doi.org/10.1016/S0960-0760(96)00184-7
  77. Liehr, J. G. (1998) Catecholestrogens in the induction of tumors in the kidney of the Syrian hamster. Adv. Pharmacol. 42, 824-828.
  78. List, H. J., Lauritsen, K. J., Reiter, R., Powers, C., Wellstein, A. and Riegel, A. T. (2001) Ribozyme targeting demonstrates that the nuclear receptor coactivator AIB1 is a rate-limiting factor for estrogendependent growth of human MCF-7 breast cancer cells. J. Biol. Chem. 276, 23763-23768. https://doi.org/10.1074/jbc.M102397200
  79. Love, R. R. and Philips, J. (2002) Oophorectomy for breast cancer: history revisited. J. Natl. Cancer Inst. 94, 1433-1434. https://doi.org/10.1093/jnci/94.19.1433
  80. Lyko, F. and Brown, R. (2005) DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J. Natl. Cancer Inst. 97, 1498-1506. https://doi.org/10.1093/jnci/dji311
  81. Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P. and Evans, R. M. (1995) The nuclear receptor superfamily: the second decade. Cell 83, 835-839. https://doi.org/10.1016/0092-8674(95)90199-X
  82. Massarweh, S. and Schiff, R. (2006) Resistance to endocrine therapy in breast cancer: exploiting estrogen receptor/growth factor signaling crosstalk. Endocr. Relat. Cancer 13 Suppl 1, S15-24. https://doi.org/10.1677/erc.1.01273
  83. Mc Ilroy, M., Fleming, F. J., Buggy, Y., Hill, A. D. and Young, L. S. (2006) Tamoxifen-induced ER-alpha-SRC-3 interaction in HER2 positive human breast cancer; a possible mechanism for ER isoform specifi c recurrence. Endocr. Relat. Cancer 13, 1135-1145. https://doi.org/10.1677/erc.1.01222
  84. McGuire, W. L., Horwitz, K. B., Pearson, O. H. and Segaloff, A. (1977) Current status of estrogen and progesterone receptors in breast cancer. Cancer 39 (6 Suppl), 2934-2947. https://doi.org/10.1002/1097-0142(197706)39:6<2934::AID-CNCR2820390680>3.0.CO;2-P
  85. Mikhaĭlov, V. M., Kropotov, A. V., Zelenin, A. V., Krutilina, R. I., Kolesnikov, V. A., Zelenina, I. A., Baranov, A. N., Shtein, G. I., Ostapenko, O. V., Tomilin, N. V. and Baranov, V. S. (2002) The BCL-xL and ACR-1 genes promote differentiation and reduce apoptosis in muscle fi bers of mdx mice. Genetika 38, 1445-1450.
  86. Mosselman, S., Polman, J. and Dijkema, R. (1996) ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett. 392, 49-53. https://doi.org/10.1016/0014-5793(96)00782-X
  87. Mouridsen, H., Giobbie-Hurder, A., Goldhirsch, A., Thürlimann, B., Paridaens, R., Smith, I., Mauriac, L., Forbes, J. F., Price, K. N., Regan, M. M., Gelber, R. D. and Coates, A. S.; BIG 1-98 Collaborative Group. (2009) Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N. Engl. J. Med. 361, 766-776. https://doi.org/10.1056/NEJMoa0810818
  88. Munzone, E., Curigliano, G., Rocca, A., Bonizzi, G., Renne, G., Goldhirsch, A. and Nole, F. (2006) Reverting estrogen-receptor-negative phenotype in HER-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy. Breast Cancer Res. 8, R4. https://doi.org/10.1186/bcr1366
  89. Murdter, T. E., Schroth, W., Bacchus-Gerybadze, L., Winter, S., Heinkele, G., Simon, W., Fasching, P. A., Fehm, T.,; German Tamoxifen and AI Clinicians Group., Eichelbaum, M., Schwab, M. and Brauch, H. (2011) Activity levels of tamoxifen metabolites at the estrogen receptor and the impact of genetic polymorphisms of phase I and II enzymes on their concentration levels in plasma. Clin. Pharmacol. Ther. 89, 708-717. https://doi.org/10.1038/clpt.2011.27
  90. Murphy, M. P. (2009) How mitochondria produce reactive oxygen species. Biochem. J. 417, 1-13. https://doi.org/10.1042/BJ20081386
  91. Myers, E., Hill, A. D., Kelly, G., McDermott, E. W., O'Higgins, N. J., Buggy, Y. and Young, L. S. (2005) ssociations and interactions between Ets-1 and Ets-2 and coregulatory proteins, SRC-1, AIB1, and NCoR in breast cancer. Clin. Cancer Res. 11, 2111-2122. https://doi.org/10.1158/1078-0432.CCR-04-1192
  92. Neumann, C. A. and Fang, Q. (2007) Are peroxiredoxins tumor suppressors? Curr. Opin. Pharmacol. 7, 375-380. https://doi.org/10.1016/j.coph.2007.04.007
  93. O'Regan, R. M., Osipo, C., Ariazi, E., Lee, E. S., Meeke, K., Morris, C., Bertucci, A., Sarker, M. A., Grigg, R. and Jordan, V. C. (2006) Development and therapeutic options for the treatment of raloxifenestimulated breast cancer in athymic mice. Clin. Cancer Res. 12, 2255-2263. https://doi.org/10.1158/1078-0432.CCR-05-2584
  94. Osborne, C. K., Bardou, V., Hopp, T. A., Chamness, G. C., Hilsenbeck, S. G., Fuqua, S. A., Wong, J., Allred, D. C., Clark, G. M. and Schiff, R. (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. https://doi.org/10.1093/jnci/95.5.353
  95. Ouhtit, A., Abd Elmageed, Z. Y., Abdraboh, M. E., Lioe, T. F. and Raj, M. H. (2007) In vivo evidence for the role of CD44s in promoting breast cancer metastasis to the liver. Am. J. Pathol. 171, 2033-2039. https://doi.org/10.2353/ajpath.2007.070535
  96. Paridaens, R. J., Dirix, L. Y., Beex, L. V., Nooij, M., Cameron, D. A., Cufer, T., Piccart, M. J., Bogaerts, J. and Therasse, P. (2008) Phase III study comparing exemestane with tamoxifen as fi rst-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J. Clin. Oncol. 26, 4883-4890. https://doi.org/10.1200/JCO.2007.14.4659
  97. Pathak, D. N., Pongracz, K. and Bodell, W. J. (1996) Activation of 4-hydroxytamoxifen and the tamoxifen derivative metabolite E by uterine peroxidase to form DNA adducts: comparison with DNA adducts formed in the uterus of Sprague-Dawley rats treated with tamoxifen. Carcinogenesis 17, 1785-1790. https://doi.org/10.1093/carcin/17.9.1785
  98. Pavlik, E. J., Nelson, K., Srinivasan, S., Powell, D. E., Kenady, D. E., DePriest, P. D., Gallion, H. H. and van Nagell, J. R. Jr. (1992) Resistance to tamoxifen with persisting sensitivity to estrogen: possible mediation by excessive antiestrogen binding site activity. Cancer Res. 52, 4106-4112.
  99. Pike, M. C., Spicer, D. V., Dahmoush, L. and Press, M. F. (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol. Rev. 15, 17-35.
  100. Qadir, M. A., Kwok, B., Dragowska, W. H., To, K. H., Le, D., Bally, M. B. and Gorski, S. M. (2008) Macroautophagy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization. Breast Cancer Res. Treat. 112, 389-403. https://doi.org/10.1007/s10549-007-9873-4
  101. Quick, E. L., Parry, E. M. and Parry, J. M. (2008) Do oestrogens induce chromosome specifi c aneuploidy in vitro, similar to the pattern of aneuploidy seen in breast cancer? Mutat. Res. 651, 46-55. https://doi.org/10.1016/j.mrgentox.2007.10.021
  102. Regan, M. M., Neven, P., Giobbie-Hurder, A., Goldhirsch, A., Ejlertsen, B., Mauriac, L., Forbes, J. F., Smith, I., Láng, I., Wardley, A., Rabaglio, M., Price, K. N., Gelber, R. D., Coates, A. S., Thürlimann, B.,; BIG 1-98 Collaborative Group; International Breast Cancer Study Group (IBCSG). (2011) Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8.1 years median follow-up. Lancet Oncol. 12, 1101-1108. https://doi.org/10.1016/S1470-2045(11)70270-4
  103. Ricketts, D. and Coombes, R. C. (1989) What's new in steroid receptor immunocytochemistry in clinical oncology? Pathol. Res. Pract. 185, 935-941. https://doi.org/10.1016/S0344-0338(89)80301-2
  104. Ring, A., Sestak, I., Baum, M., Howell, A., Buzdar, A., Dowsett, M., Forbes, J. F. and Cuzick, J. (2011) Influence of comorbidities and age on risk of death without recurrence: a retrospective analysis of the Arimidex, Tamoxifen Alone or in Combination trial. J. Clin. Oncol. 29, 4266-4272. https://doi.org/10.1200/JCO.2011.35.5545
  105. Russo, J. and Russo, I. H. (2006) The role of estrogen in the initiation of breast cancer. J. Steroid. Biochem. Mol. Biol. 102, 89-96. https://doi.org/10.1016/j.jsbmb.2006.09.004
  106. Russo, J., Ao, X., Grill, C. and Russo, I. H. (1999) Pattern of distribution of cells positive for estrogen receptor alpha and progesterone receptor in relation to proliferating cells in the mammary gland. Breast Cancer Res. Treat. 53, 217-227. https://doi.org/10.1023/A:1006186719322
  107. Russo, J., Hu, Y. F., Yang, X. and Russo, I. H. (2000) Developmental, cellular, and molecular basis of human breast cancer. J. Natl. Cancer Inst. Monogr. 27, 17-37.
  108. Russo, J., Reina, D., Frederick, J. and Russo, I. H. (1988) Expression of phenotypical changes by human breast epithelial cells treated with carcinogens in vitro. Cancer Res. 48, 2837-2857.
  109. Samaddar, J. S., Gaddy, V. T., Duplantier, J., Thandavan, S. P., Shah, M., Smith, M. J., Browning, D., Rawson, J., Smith, S. B., Barrett, J. T. and Schoenlein, P. V. (2008) A role for macroautophagy in protection against 4-hydroxytamoxifen-induced cell death and the development of antiestrogen resistance. Mol. Cancer Ther. 7, 2977-2987. https://doi.org/10.1158/1535-7163.MCT-08-0447
  110. Schiff, R., Reddy, P., Ahotupa, M., Coronado-Heinsohn, E, Grim, M., Hilsenbeck, S. G., Lawrence, R., Deneke, S., Herrera, R., Chamness, G. C., Fuqua, S. A., Brown, P. H. and Osborne, C. K. (2000) Oxidative stress and AP-1 activity in tamoxifen-resistant breast tumors in vivo. J. Natl. Cancer Inst. 92, 1926-1934. https://doi.org/10.1093/jnci/92.23.1926
  111. Schroth, W., Antoniadou, L., Fritz, P., Schwab, M., Muerdter, T., Zanger, U. M., Simon, W., Eichelbaum, M. and Brauch, H. (2007) Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J. Clin. Oncol. 25, 5187-5193. https://doi.org/10.1200/JCO.2007.12.2705
  112. Seo, M. J., Liu, X., Chang, M. and Park, J. H. (2012) GATA-binding protein 1 is a novel transcription regulator of peroxiredoxin 5 in human breast cancer cells. Int. J. Oncol. 40, 655-664.
  113. Sharma, D., Blum, J., Yang, X., Beaulieu, N., Macleod, A. R. and Davidson, N. E. (2005) Release of methyl CpG binding proteins and histone deacetylase 1 from the Estrogen receptor alpha (ER) promoter upon reactivation in ER-negative human breast cancer cells. Mol. Endocrinol. 19, 1740-1751. https://doi.org/10.1210/me.2004-0011
  114. Sheridan, C., Kishimoto, H., Fuchs, R. K., Mehrotra, S., Bhat- Nakshatri, P., Turner, C. H., Goulet, R. Jr., Badve, S. and Nakshatri, H. (2006) CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res. 8, R59. https://doi.org/10.1186/bcr1610
  115. Shiau, A. K., Barstad, D., Loria, P. M., Cheng, L., Kushner, P. J., Agard, D. A. and Greene, G. L. (1998) The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 95, 927-937. https://doi.org/10.1016/S0092-8674(00)81717-1
  116. Shou, J., Massarweh, S., Osborne, C. K., Wakeling, A. E., Ali, S., Weiss, H. and Schiff, R. (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. https://doi.org/10.1093/jnci/djh166
  117. Stearns, V., Johnson, M. D., Rae, J. M., Morocho, A., Novielli, A., Bhargava, P., Hayes, D. F., Desta, Z. and Flockhart, D. A. (2003) Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J. Natl. Cancer Inst. 95, 1758-1764. https://doi.org/10.1093/jnci/djg108
  118. Stingl, J. (2011) Estrogen and progesterone in normal mammary gland development and in cancer. Horm. Cancer 2, 85-90. https://doi.org/10.1007/s12672-010-0055-1
  119. Stoica, G. E., Franke, T. F., Moroni, M., Mueller, S., Morgan, E., Iann, M. C., Winder, A. D., Reiter, R., Wellstein, A., Martin, M. B. and Stoica, A. (2003) Effect of estradiol on estrogen receptor-alpha gene expression and activity can be modulated by the ErbB2/PI 3-K/Akt pathway. Oncogene 22, 7998-8011. https://doi.org/10.1038/sj.onc.1206769
  120. Tan, T. T. and White, E. (2008) Therapeutic targeting of death pathways in cancer: mechanisms for activating cell death in cancer cells. Adv. Exp. Med. Biol. 615, 81-104. https://doi.org/10.1007/978-1-4020-6554-5_5
  121. Tucker, A. N., Tkaczuk, K. A., Lewis, L. M., Tomic, D., Lim, C. K. and Flaws, J. A. (2005) Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 21, 61-72.
  122. Tzukerman, M. T., Esty, A., Santiso-Mere, D., Danielian, P., Parker, M. G., Stein, R. B., Pike, J. W. and McDonnell, D. P. (1994) Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions. Mol. Endocrinol. 8, 21-30. https://doi.org/10.1210/me.8.1.21
  123. van den Berg, H. W., Lynch, M., Martin, J., Nelson, J., Dickson, G. R. and Crockard, A. D. (1989) Characterisation of a tamoxifenresistant variant of the ZR-75-1 human breast cancer cell line (ZR- 75-9a1) and ability of the resistant phenotype. Br. J. Cancer 59, 522-526. https://doi.org/10.1038/bjc.1989.107
  124. Webb, P., Nguyen, P., Shinsako, J., Anderson, C., Feng, W., Nguyen, M. P., Chen, D., Huang, S. M., Subramania,n S., McKinerney, E., Katzenellenbogen, B. S., Stallcup, M. R. and Kushner, P. J. (1998) Estrogen receptor activation function 1 works by binding p160 coactivator proteins. Mol. Endocrinol. 12, 1605-1618. https://doi.org/10.1210/me.12.10.1605
  125. Wegman, P., Elingarami, S., Carstensen, J., Stål, O., Nordenskjöld, B. and Wingren, S. (2007) Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Breast Cancer Res. 9, R7. https://doi.org/10.1186/bcr1640
  126. Yager, J. D. and Davidson, N. E. (2006) Estrogen carcinogenesis in breast cancer. N. Engl. J. Med. 354, 270-282. https://doi.org/10.1056/NEJMra050776
  127. Yuan, J., Murrell, G. A., Trickett, A., Landtmeters, M., Knoops, B. and Wang, M. X. (2004) Overexpression of antioxidant enzyme peroxiredoxin 5 protects human tendon cells against apoptosis and loss of cellular function during oxidative stress. Biochim. Biophys. Acta 1693, 37-45. https://doi.org/10.1016/j.bbamcr.2004.04.006
  128. Yue, W., Wang, J. P., Li, Y., Bocchinfuso, W. P., Korach, K. S., Devanesan, P. D., Rogan, E., Cavalieri, E. and Santen, R. J. (2005) Tamoxifen versus aromatase inhibitors for breast cancer prevention. Clin. Cancer Res. 11, 925s-930s.
  129. Zajchowski, D. A., Kauser, K., Zhu, D., Webster, L., Aberle, S., White, F. A. 3rd., Liu, H. L., Humm, R., MacRobbie, J., Ponte, P., Hegele- Hartung, C., Knauthe, R., Fritzemeier, K. H., Vergona, R. and Rubanyi, G. M. (2000) Identification of selective estrogen receptor modulators by their gene expression fingerprints. J. Biol. Chem. 275, 15885-15894. https://doi.org/10.1074/jbc.M909865199
  130. Zhou, Q., Atadja, P. and Davidson, N. E. (2007) Histone deacetylase inhibitor LBH589 reactivates silenced estrogen receptor alpha (ER) gene expression without loss of DNA hypermethylation. Cancer Biol. Ther. 6, 64-69. https://doi.org/10.4161/cbt.6.1.3549

Cited by

  1. Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer vol.16, pp.1, 2016, https://doi.org/10.1186/s12885-016-2452-5
  2. Application of pharmacometrics and quantitative systems pharmacology to cancer therapy: The example of luminal a breast cancer vol.124, 2017, https://doi.org/10.1016/j.phrs.2017.07.015
  3. An in vitro model for the development of acquired tamoxifen resistance vol.32, pp.6, 2016, https://doi.org/10.1007/s10565-016-9355-8
  4. The emerging role of zinc transporters in cellular homeostasis and cancer vol.2, 2017, https://doi.org/10.1038/sigtrans.2017.29
  5. The role of IL17B-IL17RB signaling pathway in breast cancer vol.88, 2017, https://doi.org/10.1016/j.biopha.2017.01.120
  6. MUC1 induces tamoxifen resistance in estrogen receptor-positive breast cancer vol.17, pp.7, 2017, https://doi.org/10.1080/14737140.2017.1340837
  7. Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications vol.158, pp.2, 2016, https://doi.org/10.1007/s10549-016-3876-y
  8. Nuclear and extranuclear-initiated estrogen receptor signaling crosstalk and endocrine resistance in breast cancer vol.114, 2016, https://doi.org/10.1016/j.steroids.2016.06.007
  9. Down–regulation of cyclin–dependent kinase-4 and MAPK through estrogen receptor mediated cell cycle arrest in human breast cancer induced by gold nanoparticle tagged toxin protein NKCT1 vol.268, 2017, https://doi.org/10.1016/j.cbi.2017.03.009
  10. β-Thujaplicin modulates estrogen receptor signaling and inhibits proliferation of human breast cancer cells vol.79, pp.6, 2015, https://doi.org/10.1080/09168451.2015.1008978
  11. The Effect of Newly Synthesized Heterosteroids on miRNA34a, 98, and 214 Expression Levels in MCF-7 Breast Cancer Cells 2017, https://doi.org/10.1007/s12291-017-0681-2
  12. MCAM/CD146 promotes tamoxifen resistance in breast cancer cells through induction of epithelial–mesenchymal transition, decreased ERα expression and AKT activation vol.386, 2017, https://doi.org/10.1016/j.canlet.2016.11.004
  13. Dithiiranylmethyloxy azaxanthone shows potent anti-tumor activity via suppression of HER2 expression and HER2-mediated signals in HER2-overexpressing breast cancer cells vol.50, pp.2, 2013, https://doi.org/10.1016/j.ejps.2013.06.014
  14. Protein Kinase Targets in Breast Cancer vol.18, pp.12, 2017, https://doi.org/10.3390/ijms18122543
  15. Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha vol.10, pp.4, 2017, https://doi.org/10.3390/ph10040081
  16. Nonsteroidal estrogen receptor isoform-selective biphenyls vol.91, pp.2, 2017, https://doi.org/10.1111/cbdd.13126
  17. Fundamentals of siRNA and miRNA therapeutics and a review of targeted nanoparticle delivery systems in breast cancer vol.10, pp.1, 2018, https://doi.org/10.1007/s12551-017-0392-1
  18. Multi-drug resistance protein 2 (MRP2) expression, adjuvant tamoxifen therapy, and risk of breast cancer recurrence: a Danish population-based nested case-control study pp.1651-226X, 2018, https://doi.org/10.1080/0284186X.2018.1537508
  19. Chimeric HDAC inhibitors: Comprehensive review on the HDAC-based strategies developed to combat cancer vol.38, pp.6, 2018, https://doi.org/10.1002/med.21505
  20. AhR ligand aminoflavone suppresses α6-integrin-Src-Akt signaling to attenuate tamoxifen resistance in breast cancer cells vol.234, pp.1, 2018, https://doi.org/10.1002/jcp.27013
  21. Cell cycle–dependent force transmission in cancer cells vol.29, pp.21, 2018, https://doi.org/10.1091/mbc.E17-12-0726
  22. Nonhormonal selective estrogen receptor modulator 1-(2-[4-{(3R,4S)-7-Methoxy-2, 2-dimethyl-3-phenyl-chroman-4yl}phenoxy]ethyl)pyrrolidine hydrochloride (ormeloxifene hydrochloride) for the treatment of breast cancer vol.79, pp.6, 2018, https://doi.org/10.1002/ddr.21440
  23. The mTOR inhibitor AZD8055 overcomes tamoxifen resistance in breast cancer cells by down-regulating HSPB8 vol.39, pp.8, 2018, https://doi.org/10.1038/aps.2017.181
  24. Therapeutic potential of melatonin for breast cancer radiation therapy patients vol.94, pp.5, 2018, https://doi.org/10.1080/09553002.2018.1446227
  25. BP1, a potential biomarker for breast cancer prognosis vol.12, pp.5, 2018, https://doi.org/10.2217/bmm-2017-0212
  26. Enhanced ZnR/GPR39 Activity in Breast Cancer, an Alternative Trigger of Signaling Leading to Cell Growth vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-26459-5
  27. Interplay between Epigenetics, Expression of Estrogen Receptor- α, HER2/ERBB2 and Sensitivity of Triple Negative Breast Cancer Cells to Hormonal Therapy vol.11, pp.1, 2018, https://doi.org/10.3390/cancers11010013
  28. Liquid biopsy in breast cancer: A comprehensive review pp.00099163, 2019, https://doi.org/10.1111/cge.13514
  29. SNAIL is induced by tamoxifen and leads to growth inhibition in invasive lobular breast carcinoma pp.1573-7217, 2019, https://doi.org/10.1007/s10549-019-05161-8
  30. p21-activated kinase group II small compound inhibitor GNE-2861 perturbs estrogen receptor alpha signaling and restores tamoxifen-sensitivity in breast cancer cells vol.6, pp.41, 2012, https://doi.org/10.18632/oncotarget.6081
  31. Induction of UDP-Glucuronosyltransferase 2B15 Gene Expression by the Major Active Metabolites of Tamoxifen, 4-Hydroxytamoxifen and Endoxifen, in Breast Cancer Cells vol.43, pp.6, 2015, https://doi.org/10.1124/dmd.114.062935
  32. CIP2A expression predicts recurrences of tamoxifen-treated breast cancer vol.39, pp.10, 2012, https://doi.org/10.1177/1010428317722064
  33. Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer vol.61, pp.7, 2018, https://doi.org/10.1021/acs.jmedchem.7b01682
  34. Energy Metabolism Drugs Block Triple Negative Breast Metastatic Cancer Cell Phenotype vol.15, pp.6, 2018, https://doi.org/10.1021/acs.molpharmaceut.8b00015
  35. Cell Division Cycle Associated 8 Is a Key Regulator of Tamoxifen Resistance in Breast Cancer vol.22, pp.2, 2012, https://doi.org/10.4048/jbc.2019.22.e29
  36. Antiproliferative Effect of Trifolium Pratens L. Extract in Human Breast Cancer Cells vol.71, pp.1, 2012, https://doi.org/10.1080/01635581.2018.1521443
  37. Novel Diphenylamine Analogs Induce Mesenchymal to Epithelial Transition in Triple Negative Breast Cancer vol.9, pp.None, 2012, https://doi.org/10.3389/fonc.2019.00672
  38. Involvement of miR-770-5p in trastuzumab response in HER2 positive breast cancer cells vol.14, pp.4, 2019, https://doi.org/10.1371/journal.pone.0215894
  39. Molecular insights into cancer drug resistance from a proteomics perspective vol.16, pp.5, 2019, https://doi.org/10.1080/14789450.2019.1601561
  40. BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation vol.25, pp.None, 2012, https://doi.org/10.1590/1678-9199-jvatitd-2019-0010
  41. 1,2,4-Oxadiazole-5-ones as analogues of tamoxifen: synthesis and biological evaluation vol.17, pp.19, 2012, https://doi.org/10.1039/c9ob00651f
  42. Pharmacological, Mechanistic, and Pharmacokinetic Assessment of Novel Melatonin-Tamoxifen Drug Conjugates as Breast Cancer Drugs vol.96, pp.2, 2012, https://doi.org/10.1124/mol.119.116202
  43. Modulation of Burst Firing of Neurons in Nucleus Reticularis of the Thalamus by GluN2C-Containing NMDA Receptors vol.96, pp.2, 2012, https://doi.org/10.1124/mol.119.116780
  44. Moonlighting Proteins and Cardiopathy in the Spatial Response of MCF‐7 Breast Cancer Cells to Tamoxifen vol.13, pp.5, 2012, https://doi.org/10.1002/prca.201900029
  45. Overcoming Tamoxifen Resistance by Regulation of Del-1 in Breast Cancer vol.97, pp.3, 2012, https://doi.org/10.1159/000501340
  46. Involvement of the P2X7 receptor in the migration and metastasis of tamoxifen-resistant breast cancer: effects on small extracellular vesicles production vol.9, pp.1, 2019, https://doi.org/10.1038/s41598-019-47734-z
  47. The Potential Role of Claudins in Regulation of Metastasis and Development of Drug Resistance in Breast Cancer vol.7, pp.1, 2020, https://doi.org/10.2174/2212697x06666191021121022
  48. IGFBP-1 Expression Promotes Tamoxifen Resistance in Breast Cancer Cells via Erk Pathway Activation vol.11, pp.None, 2012, https://doi.org/10.3389/fendo.2020.00233
  49. Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma vol.9, pp.3, 2012, https://doi.org/10.3390/cells9030614
  50. Overcoming tamoxifen resistance in oestrogen receptor‐positive breast cancer using the novel thiosemicarbazone anti‐cancer agent, DPC vol.177, pp.10, 2020, https://doi.org/10.1111/bph.14985
  51. Synthesis of novel flexible tamoxifen analogues to overcome CYP2D6 polymorphism and their biological evaluation on MCF‐7 cell line vol.81, pp.4, 2020, https://doi.org/10.1002/ddr.21637
  52. The Network of Angiotensin Receptors in Breast Cancer vol.9, pp.6, 2012, https://doi.org/10.3390/cells9061336
  53. Incidence of Hyperglycemia/Secondary Diabetes in Women who have Undergone Curative Chemotherapy for Breast Cancer: First Study from India vol.9, pp.3, 2012, https://doi.org/10.1055/s-0041-1723104
  54. Chemical Composition of Essential Oil of Garcinia gummi-gutta and Its Antimicrobial and Cytotoxic Activities vol.23, pp.4, 2020, https://doi.org/10.1080/0972060x.2020.1828179
  55. Recent Advances in the Synthesis of Tamoxifen and Analogues in Medicinal Chemistry vol.9, pp.10, 2012, https://doi.org/10.1002/ajoc.202000308
  56. Point-activated ESR1Y541S has a dramatic effect on the development of sexually dimorphic organs vol.34, pp.19, 2012, https://doi.org/10.1101/gad.339424.120
  57. Progesterone receptor membrane component 1 promotes the growth of breast cancers by altering the phosphoproteome and augmenting EGFR/PI3K/AKT signalling vol.123, pp.8, 2012, https://doi.org/10.1038/s41416-020-0992-6
  58. Recent progress on HDAC inhibitors with dual targeting capabilities for cancer treatment vol.208, pp.None, 2012, https://doi.org/10.1016/j.ejmech.2020.112831
  59. Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub-phenotype ex vivo vol.10, pp.1, 2020, https://doi.org/10.1038/s41598-020-75779-y
  60. Adenylate Kinase 4 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an m6A-Based Epitranscriptomic Mechanism vol.28, pp.12, 2012, https://doi.org/10.1016/j.ymthe.2020.09.007
  61. Selective Estrogen Receptor Degraders (SERDs): A Promising Strategy for Estrogen Receptor Positive Endocrine-Resistant Breast Cancer vol.63, pp.24, 2020, https://doi.org/10.1021/acs.jmedchem.0c00913
  62. Synthesis, characterization and molecular docking of new gold complexes as a breast anticancer vol.45, pp.p6, 2012, https://doi.org/10.1016/j.matpr.2021.02.383
  63. Resuming Sensitivity of Tamoxifen-Resistant Breast Cancer Cells to Tamoxifen by Tetrandrine vol.20, pp.None, 2012, https://doi.org/10.1177/1534735421996822
  64. In Silico Screening of Marine Compounds as an Emerging and Promising Approach against Estrogen Receptor Alpha-Positive Breast Cancer vol.2021, pp.None, 2012, https://doi.org/10.1155/2021/9734279
  65. Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer vol.891, pp.None, 2021, https://doi.org/10.1016/j.ejphar.2020.173697
  66. Molecular Mechanisms of Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer vol.12, pp.None, 2012, https://doi.org/10.3389/fendo.2021.599586
  67. Impact of sex hormones dysregulation and adiposity on the outcome of postmenopausal breast cancer patients vol.11, pp.1, 2012, https://doi.org/10.1111/cob.12423
  68. Synthesis and Biological Evaluation of 1-(Diarylmethyl)-1H-1,2,4-triazoles and 1-(Diarylmethyl)-1H-imidazoles as a Novel Class of Anti-Mitotic Agent for Activity in Breast Cancer vol.14, pp.2, 2012, https://doi.org/10.3390/ph14020169
  69. Novel Biphenyl Amines Inhibit Oestrogen Receptor (ER)-α in ER-Positive Mammary Carcinoma Cells vol.26, pp.4, 2021, https://doi.org/10.3390/molecules26040783
  70. Plasmin and Plasminogen System in the Tumor Microenvironment: Implications for Cancer Diagnosis, Prognosis, and Therapy vol.13, pp.8, 2012, https://doi.org/10.3390/cancers13081838
  71. Breast Cancer Response to Therapy: Can microRNAs Lead the Way? vol.26, pp.2, 2012, https://doi.org/10.1007/s10911-021-09478-3
  72. Development and Characterization of Novel Endoxifen-Resistant Breast Cancer Cell Lines Highlight Numerous Differences from Tamoxifen-Resistant Models vol.19, pp.6, 2012, https://doi.org/10.1158/1541-7786.mcr-20-0872
  73. TNFα Enhances Tamoxifen Sensitivity through Dissociation of ERα-p53-NCOR1 Complexes in ERα-Positive Breast Cancer vol.13, pp.11, 2012, https://doi.org/10.3390/cancers13112601
  74. Pharmacological Inhibition of CBP/p300 Blocks Estrogen Receptor Alpha (ERα) Function through Suppressing Enhancer H3K27 Acetylation in Luminal Breast Cancer vol.13, pp.11, 2012, https://doi.org/10.3390/cancers13112799
  75. CBP/p300: Critical Co-Activators for Nuclear Steroid Hormone Receptors and Emerging Therapeutic Targets in Prostate and Breast Cancers vol.13, pp.12, 2012, https://doi.org/10.3390/cancers13122872
  76. Collagen I Fibrous Substrates Modulate the Proliferation and Secretome of Estrogen Receptor-Positive Breast Tumor Cells in a Hormone-Restricted Microenvironment vol.7, pp.6, 2012, https://doi.org/10.1021/acsbiomaterials.0c01803
  77. ATF3 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an N6-Methyladenosine-Based Epitranscriptomic Mechanism vol.34, pp.7, 2012, https://doi.org/10.1021/acs.chemrestox.1c00206
  78. GDC-9545 (Giredestrant): A Potent and Orally Bioavailable Selective Estrogen Receptor Antagonist and Degrader with an Exceptional Preclinical Profile for ER+ Breast Cancer vol.64, pp.16, 2012, https://doi.org/10.1021/acs.jmedchem.1c00847
  79. The effect of IL-1β on MRP2 expression and tamoxifen toxicity in MCF-7 breast cancer cells vol.40, pp.4, 2012, https://doi.org/10.3233/bd-201056
  80. Targeting Estrogen Receptor-Positive Breast Microtumors with Endoxifen-Conjugated, Hypoxia-Sensitive Polymersomes vol.6, pp.42, 2021, https://doi.org/10.1021/acsomega.1c02250
  81. Role of TGF-β signaling in the mechanisms of tamoxifen resistance vol.62, pp.None, 2012, https://doi.org/10.1016/j.cytogfr.2021.09.005
  82. microRNA-221 and tamoxifen resistance in luminal-subtype breast cancer patients: A case-control study vol.73, pp.None, 2022, https://doi.org/10.1016/j.amsu.2021.103092