Perspectives of pharmacogenetics approach to personalized tamoxifen therapy


如何引用文章

全文:

详细

Tamoxifen is a selective modulator of estrogen receptors and is widely used in receptor-a-positive breast cancer treatment. Adjuvant tamoxifen treatment substantially reduces breast cancer relapse and mortality rates. However, high interindividual variability in response is observed. One of the causes of this variability may be genetic polymorphisms of the cytochrome P450 (CYP) enzymes, which are responsible for the formation of tamoxifen active metabolites. Polymorphisms of genes encoding the enzymes with decreased or absent activity could be associated with lower tamoxifen active metabolites concentration in serum and consequently reduce the effectiveness of treatment. Pharmacogenetic approach is a promising tool of personalized medicine and may help personolize pharmacotherapy of breast cancer in the future. Throughout this review we analyze the up-to-date information on the influence of the gene CYP2C19 polymorphisms that they have on pharmacokinetic and pharmacodynamic of tamoxifen.

作者简介

M Savelyeva

Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation; I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

Email: marinasavelyeva@mail.ru
д-р мед. наук, проф. каф. клин. фармакологии и терапии ФГБОУ ДПО РМАНПО, проф. каф. патологии человека ФГАОУ ВО «Первый МГМУ им. И.М.Сеченова 125993, Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1; 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2

A Ignatova

I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

студентка 4-го курса фак-та «Медицина будущего» ФГАОУ ВО «Первый МГМУ им. И.М.Сеченова» 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2

Yu Panchenko

I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

студентка 4-го курса фак-та «Медицина будущего» ФГАОУ ВО «Первый МГМУ им. И.М.Сеченова» 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2

I Urvantseva

I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

студентка 4-го курса фак-та «Медицина будущего» ФГАОУ ВО «Первый МГМУ им. И.М.Сеченова» 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2

I Poddubnaya

Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation

акад. РАН, д-р мед. наук, проф., зав. каф. онкологии, проректор по учебной работе и международному сотрудничеству ФГБОУ ДПО РМАНПО 125993, Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1

参考

  1. Burstein H.J, Griggs J.J, Prestrud A.A, Temin S. American Society of Clinical Oncology clinical practice guideline update on adjuvant endocrine therapy for women with hormone receptor - positive breast cancer. J Oncol Pract 2010; 6 (5): 243-6.
  2. Forrest A.R. Aromatase inhibitors in breast cancer. N Engl J Med 2003; 349: 1090.
  3. Early Breast Cancer Trialists' Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998; 351: 1451-67.
  4. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687-717.
  5. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient - level meta - analysis of randomised trials. Lancet 2011; 378: 771-84.
  6. Lim Y.C, Desta Z, Flockhart D.A, Skaar T.C. Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti - estrogenic effects in breast cancer cells with potency similar to 4-hydroxy - tamoxifen. Cancer Chemother Pharmacol 2005; 55: 471-8.
  7. Johnson M.D1, Zuo H, Lee K.H et al. Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat 2004; 85: 151-9.
  8. Desta Z, Ward B.A, Soukhova N.V, Flockhart D.A. Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther 2004; 310: 1062-75.
  9. NCCN Clinical Practice Guidelines in Oncology. Breast cancer version 2.2017 - April 6, 2017.
  10. Jin Y, Desta Z, Stearns V et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005; 97:30-9.
  11. Borges S, Desta Z, Li L et al. Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 2006; 80: 61-74.
  12. Schroth W, Antoniadou L, Fritz P et al. Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol 2007; 25: 5187-93.
  13. Brauch H, Mürdter T.E, Eichelbaum M, Schwab M. Pharmacogenomics of tamoxifen therapy. Clin Chem 2009; 55: 1770-82.
  14. Desta Z, Ward B.A, Soukhova N.V, Flockhart D.A. Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther 2004; 310: 1062-75.
  15. Brauch H, Mürdter T.E, Eichelbaum M, Schwab M. Pharmacogenomics of Tamoxifen Therapy. Clinical Chemistry 2009; 55 (10): 1770-82.
  16. Human cytochrome P450 (CYP) allele nomenclature T. The Human Cytochrome P450 (CYP) Allele Nomenclature Database.
  17. Gjerde J, Geisler J, Lundgren S et al. Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer. BMC Cancer 2010; 10: 313.
  18. Zafra-Ceres M, de Haro T, Farez-Vidal E et al. Influence of CYP2D6 Polymorphisms on Serum Levels of Tamoxifen Metabolites in Spanish Women with Breast Cancer. Int J Med Sci 2013; 10: 932-7.
  19. Powers J.L, Buys S.S, Fletcher D et al. Multigene and Drug Interaction Approach for Tamoxifen Metabolite Patterns Reveals Possible Involvement of CYP2C9, CYP2C19, and ABCB1. J Clin Pharmacol 2016; 56: 1570-81.
  20. Lim J.S, Chen X.A, Singh O et al. Impact of CYP2D6, CYP3A5, CYP2C9 and CYP2C19 polymorphisms on tamoxifen pharmacokinetics in Asian breast cancer patients. Br J Clin Pharmacol 2011; 71: 737-50.
  21. Mürdter T.E, Schroth W, Bacchus-Gerybadze L et al; German Tamoxifen and AI Clinicians Group, Eichelbaum M, Schwab M, Brauch H. 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 2011; 89: 708-17.
  22. Saladores P, Mürdter T, Eccles D et al. Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Pharmacogenomics J 2015; 15: 84-94.
  23. Lim J.S, Sutiman N, Muerdter T.E et al. Association of CYP2C19*2 and associated haplotypes with lower norendoxifen concentrations in tamoxifen - treated Asian breast cancer patients. Br J Clin Pharmacol 2016; 81: 1142-52.
  24. Lu W.J, Desta Z, Flockhart D.A. Tamoxifen metabolites as active inhibitors of aromatase in the treatment of breast cancer. Breast Cancer Res Treat 2012; 131: 473-81.
  25. Lu W.J, Xu C, Pei Z et al. The tamoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents. Breast Cancer Res Treat 2012; 133: 99-109.
  26. Lv W.J, Liu J, Lu D et al. Synthesis of mixed (E,Z)-, (E)-, and (Z)-norendoxifen with dual aromatase inhibitory and estrogen receptor modulatory activities. J Med Chem 2013; 56: 4611-8.
  27. Wei Lv, Jinzhong Liu, Skaar T.C et al. Design and Synthesis of Norendoxifen Analogues with Dual Aromatase Inhibitory and Estrogen Receptor Modulatory Activities. J Med Chem 2015; 58: 2623-48.
  28. Okishiro M, Taguchi T, Jin Kim S et al. Genetic polymorphisms of CYP2D6 10 and CYP2C19 2, 3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen. Cancer 2009; 1 (115): 952-61.
  29. Mwinyi J, Vokinger K, Jetter A et al. Impact of variable CYP genotypes on breast cancer relapse in patients undergoing adjuvant tamoxifen therapy. Cancer Chemother Pharmacol 2014; 73: 1181-8.
  30. Moyer A.M, Suman V.J, Weinshilboum R.M et al. SULT1A1, CYP2C19 and disease - free survival in early breast cancer patients receiving tamoxifen. Pharmacogenomics 2011; 12: 1535-43.
  31. Chamnanphon M, Pechatanan K, Sirachainan E et al. Association of CYP2D6 and CYP2C19 polymorphisms and disease - free survival of Thai post - menopausal breast cancer patients who received adjuvant tamoxifen. Pharmgenomics Pers Med 2013; 6: 37-48.
  32. Ruiter R, Bijl M.J, van Schaik R.H et al. CYP2C19*2 polymorphism is associated with increased survival in breast cancer patients using tamoxifen. Pharmacogenomics 2010; 11: 1367-75.
  33. Beelen K, Opdam M, Severson T.M et al. CYP2C19*2 predicts substantial tamoxifen benefit in postmenopausal breast cancer patients randomized between adjuvant tamoxifen and no systemic treatment. Breast Cancer Res Treat 2013; 139: 649-55.
  34. Schroth W, Antoniadou L, Fritz P et al. Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol 2007; 25: 5187-93.
  35. Schaik R.H, Kok M, Sweep F.C et al. The CYP2C19*2 genotype predicts tamoxifen treatment outcome in advanced breast cancer patients. Pharmacogenomics 2011; 12: 1137-46.
  36. Bai L, He J, He G.H et al. Association of CYP2C19 polymorphisms with survival of breast cancer patients using tamoxifen: results of a meta - analysis. Asian Pac J Cancer Prev 2014; 15: 8331-5.
  37. Justenhoven C, Hamann U, Pierl C.B et al. CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat 2009; 115: 391-6.

版权所有 © Consilium Medicum, 2017

Creative Commons License
此作品已接受知识共享署名-非商业性使用 4.0国际许可协议的许可。
 


##common.cookie##