Фармакогенетическое тестирование аллельных вариантов гена CYP2D6 при гормоноположительном раке молочной железы

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Тамоксифен является препаратом выбора при эндокринотерапии гормоноположительного рака молочной железы у женщин в репродуктивном возрасте. Метаболическая активность тамоксифена в организме определяется активностью фермента CYP2D6, кодируемого одноименным геном: под действием фермента тамоксифен переходит в метаболически активную форму – эндоксифен. Фармакогенетическое тестирование гена CYP2D6 у пациентов с гормоноположительным раком молочной железы поможет прогнозировать эффективность терапии и оценить риск развития побочных эффектов в целях улучшения отдаленных результатов лечения.

Об авторах

Л. Н. Любченко

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России.

Автор, ответственный за переписку.
Email: clingen@mail.ru
115478 Москва, Каширское шоссе, 24. Россия

М. Г. Филиппова

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России.

Email: fake@neicon.ru
115478 Москва, Каширское шоссе, 24. Россия

Т. А. Шендрикова

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России.

Email: fake@neicon.ru
115478 Москва, Каширское шоссе, 24. Россия

Л. Г. Жукова

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России.

Email: fake@neicon.ru
115478 Москва, Каширское шоссе, 24. Россия

Н. И. Мехтиева

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России.

Email: fake@neicon.ru
115478 Москва, Каширское шоссе, 24. Россия

О. В. Крохина

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России.

Email: fake@neicon.ru
115478 Москва, Каширское шоссе, 24. Россия

С. М. Портной

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России.

Email: fake@neicon.ru
115478 Москва, Каширское шоссе, 24. Россия

Список литературы

  1. Статистика злокачественных новообразований в России и странах СНГ в 2012 г. Под ред. М.И. Давыдова, Е.М. Аксель М.: Издательская группа РОНЦ, 2014. 226 с. [Statistics of malignant neoplasms in Russia and CIS countries in 2012. Eds.: M.I. Davydov, E.M. Axel’. Moscow: Izdatel’skaya gruppa RONTS, 2014. 226 p. (In Russ.)].
  2. McGraw J., Waller D. Cytochrome P450 variations in different ethnic populations. Expert Opin Drug Metab Toxicol 2012;8(3):371–82.
  3. Gonzalez F.J., Mackenzie P.I., Kimura S., Nebert D.W. Isolation and characterization of mouse full-length cDNA and genomic clones of 3-methylcholanthreneinducible cytochrome P1-450 and P3-450. Gene 1984;29(3):281–92.
  4. Nebert D.W., Adesnik M., Coon M.J. et al. The P450 gene superfamily: recommended nomenclature. DNA 1987;6(1):1–11.
  5. Nelson D.R. Cytochrome P450 gene superfamily. Available at: drnelson.utmem. edu/cytochromeP450.html (Accessed July 10, 2002).
  6. Phillips K.A., Veenstra D.L., Oren E. et al. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA 2001;286(18):2270–9.
  7. Andersson T., Flockhart D.A., Goldstein D.B. et al. Drug-metabolizing enzymes: evidence for clinical utility of pharmacogenomic tests. Clin Pharmacol Ther 2005;78(6):559–81.
  8. Franceschi M., Scarcelli C., Niro V. et al. Prevalence, clinical features and avoidability of adverse drug reactions as cause of admission to a geriatric unit: a prospective study of 1756 patients. Drug Saf 2008;31(6):545–56.
  9. Lazarou J., Pomeranz B.H., Corey P.N. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279(15):1200–5.
  10. Goldhirsch А., Wood W.C., Gelber R.D. et. al Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer. Ann Oncol 2007;18(7):1133–44.
  11. Davies C., Pan H., Godwin J. et al. Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomized trial. Lancet 2013;381(9869):805–16.
  12. Gray R.G., Rea D.W., Handley K. et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol 2013;31(18S):5.
  13. Lim Y.C., Desta Z., Flockhart D.A., Skaar T.C. Endoxifen (4-hydroxy-N-desmethyltamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxytamoxifen. Cancer Chemother Pharmacol 2005;55(5):471–8.
  14. Crewe H.K., Ellis S.W., Lennard M.S., Tucker GT. Variable contribution of cytochromes P450 2D6, 2C9 and 3A4 to the 4-hydroxylation of tamoxifen by human liver microsomes. Biochem Pharmacol 1997;53(2):171–8.
  15. Murdter T.E., Schroth W., Bacchus-Gerybadze L. et al. 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(5):708–17.
  16. Wu X., Hawse J.R., Subramaniam M. et al. The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells. Cancer Res 2009;69(5):1722–7.
  17. de Vries Schultink A.H., Zwart W., Linn S.C. et al. Effects of pharmacogenetics on the pharmacokinetics and pharmacodynamics of tamoxifen. Clin Pharmacokinet 2015;54(8):797–810.
  18. 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(6):1181–8.
  19. Eichelbaum M., Ingelman-Sundberg M., Evans W.E. Pharmacogenomics and individualized drug therapy. Annu Rev Med 2006;57:119–37.
  20. Evans W.E., Relling M.V. Pharmacogenomics: translating functional genomics into rational therapeutics. Science1999;286(5439):487–91.
  21. Nebert D.W., Jorge-Nebert L.F. Pharmacogenetics and pharmacogenomics. In book: Emery and rimoin’s principles and practice of medical genetics. 4th edn. Eds.: D.L. Rimoin, J.M. Connor, R.E . Pyeritz, B.R. Korf. Edinburgh: Harcourt Brace, 2002. Pp. 590–631.
  22. Crewe H.K., Notley L.M., Wunsch R.M. et al. Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 40 -hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metabolism Dispos 2002;30(8):869–74.
  23. 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(3):1062–75.
  24. Maximov P.Y., McDaniel R.E., Fernandes D.J. et al. Simulation with cells in vitro of tamoxifen treatment in premenopausal breast cancer patients with different CYP2D6 genotypes. Br J Pharmacol 2014;171(24):5624–35.
  25. Johnson M.D., 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(2):151–9.
  26. Bradford L.D. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics 2001;3(2):229–43.
  27. Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J 2005;5(1):6–13.
  28. Zanger U.M., Raimundo S., Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol 2004;369(1):23–37.
  29. Goetz M.P., Rae J.M., Suman V.J. et al. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 2005;23(36):9312–8.
  30. Human cytochrome P450 (CYP) allele nomenclature T. The Human Cytochrome P450 (CYP) Allele Nomenclature Data base. Available at: www.cypalleles.ki.se/cyp2d6.htm. (Accessed Dec 28, 2014).
  31. Gaikovitch E.A., Cascorbi I., Mrozikiewicz P.M. et al. Polymorphisms of drugmetabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2 and of P-glycoprotein in a Russian population. Eur J Clin Pharmacol 2003;59(4):303–12.
  32. Кольман Я., Рём К.Г. Наглядная биохимия. М.: Мир, 2000. 470 c. [Kohl’mann I., Rem K.G. Visible biochemistry. Moscow: Mir, 2000. 470 p. (In Russ.)].
  33. Сычев Д.А., Миронова Н.А. Фармакогенетическое тестирование по CYP2D6 и CYP2C19: значение для персонализации применения лекарственных средств в клинической практике. Лаборатория 2012;(4):11–3. [Sychev D.A., Mironova N.A. Pharmacogenetic testing for CYP2D6 and CYP2C19: a value for personalizing the use of drugs in clinical practice. Laboratoriya = Laboratory 2012;(4):11–3. (In Russ.)].
  34. Zhou S.F. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. Clin Pharmacokinet 2009;48(12):761–804.
  35. 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 2006;80(1):61–74.
  36. Lim H.S., Ju Lee H., Seok Lee K. et al. Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer. J Clin Oncol 2007;25(25):3837–45.
  37. Madlensky L., Natarajan L., Tchu S. et al. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther 2011;89(5):718–25.
  38. Schroth W., Goetz M.P., Hamann U. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 2009;302(13):1429–36.
  39. Regan M., Leyland-Jones B., Bouzyk M. et al. CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the Breast International Group 1-98 trial. J Natl Cancer Inst 2012;104(6):441–51.
  40. Rae J.M., Drury S., Hayes D.F. et al. ATAC trialists: CYP2D6and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst 2012;104(6):452–60.
  41. Nakamura Y., Ratain M.J., Cox N.J. CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the Breast International Group 1-98 trial. J Natl Cancer Inst 2012;104(16):1264.
  42. Dezentjé V.O., van Schaik R.H., VletterBogaartz J.M. et al. CYP2D6 genotype in relation to tamoxifen efficacy in a Dutch cohort of the tamoxifen exemestane adjuvantmultinational (TEAM) trial. Breast Cancer Res Treat 2013;140(2):363–73.
  43. Goetz M.P., Suman V.J., Hoskin T.L. et al. CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8. Clin Cancer Res 2013;19(2):500–7.
  44. Karle J., Bolbrinker J., Vogl S. et al. Influence of CYP2D6-genotype on tamoxifen efficacy in advanced breast cancer. Breast Cancer Res Treat 2013;139(2):553–60.
  45. Zeng Z., Liu Y., Liu Z. CYP2D6 polymorphisms influence tamoxifen treatment outcomes in breast cancer patients: a metaanalysis. Cancer Chemother Pharmacol 2013;72(2):287–303.
  46. Irvin W.J. Jr, Walko C.M., Weck K.E. et al. Genotype-guided tamoxifen dosing increases active metabolite exposure in women with reduced CYP2D6 metabolism: a multicenter study. J Clin Oncol 2011;29(24):3232–9.
  47. Kiyotani K., Mushiroda T., Imamura C.K. at al. Dose-adjustment study of tamoxifen based on CYP2D6 genotypes in Japanese breast cancer patients. Breast Cancer Res Treat 2012;131(1):137–45.
  48. Rolla R., Vidali M., Meola S. et al. Side effects associated with ultrarapid cytochrome P450 2D6 genotype among women with early stage breast cancer treated with tamoxifen. Clin Lab 2012;58(11–12): 1211–8.
  49. Barginear M.F., Jaremko M., Peter I. et al. Increasing tamoxifen dose in breast cancer patients based on CYP2D6 genotypes and endoxifen levels: effect on active metabolite isomers and the antiestrogenic activity score. Clin Pharmacol Ther 2011;90(4):605–11.
  50. Brauch H., Schroth W., Goetz M.P. et al. Tamoxifen use in postmenopausal breast cancer: CYP2D6 matters. J Clin Oncol 2013;31(2):176–80.
  51. Fann J.R., Thomas-Rich A.M., Katon W.J. et al. Major depression after breast cancer: a review of epidemiology and treatment. Gen Hosp Psychiatry 2008;30(2):112–26.
  52. Jeppesen U., Gram L.F., Vistisen K. et al. Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine. Eur J Clin Pharmacol 1996;51(1):73–8.
  53. Binkhorst L., Bannink M., de Bruijn P. et al. Augmentation of endoxifen exposure in tamoxifen-treated women following SSRI switch. Clin Pharmacokinet 2016;55(2):249–55.
  54. Borges S., Desta Z., Jin Y. et al. Composite functional genetic and comedication CYP2D6 activity score in predicting tamoxifen drug exposure among breast cancer patients. J Clin Pharmacol 2010;50(4):450–8.
  55. 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(1):30–9.
  56. Stearns V., Johnson M.D., Rae J.M. et al. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 2003;95(23):1758–64.
  57. Chubak J., Buist D.S., Boudreau D.M. et al. Breast cancer recurrence risk in relation to antidepressant use after diagnosis. Breast Cancer Res Treat 2008;112(1):123–32.
  58. Lehmann D., Nelsen J., Ramanath V. et al. Lack of attenuation in the antitumor effect of tamoxifen by chronic CYP isoform inhibition. J Clin Pharmacol 2004;44(8):861–5.
  59. Stingl J.C., Parmar S., Huber-Wechselberger A. et al. Impact of CYP2D6*4 geno type on progression free survival in tamoxifen breast cancer treatment. Curr Med Res Opin 2010;26(11):2535–42.
  60. Bijl M.J., van Schaik R.H., Lammers L.A. et al. The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users. Breast Cancer Res Treat 2009;118(1):125–30.
  61. 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(33):5187–93.
  62. Martins D.M., Vidal F.C., Souza R.D. et al. Determination of CYP2D6 *3, *4, and *10 frequency in women with breast cancer in São Luís, Brazil, and its association with prognostic factors and diseasefree survival. Braz J Med Biol Res 2014;47(11):1008–15.
  63. Nowell S., Ahn J., Rae J.M. et al. Association of genetic variation in tamoxifen-metabolizing enzymes with overall survival and recurrence of disease in breast cancer patients. Breast Cancer Res Treat 2005;91(3):249–58.
  64. Wegman P., Elingarami S., Carstensen J. et al. Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Breast Cancer Res 2007;9(1):7.
  65. Swen J.J., Nijenhuis M., de Boer A. Pharmacogenetics: from bench to byte – an update of guidelines. Clin Pharmacol Ther 2011;89(5):662–73.
  66. Tamoxifen background summary Draft. Available at: www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4248b1-01-fdatamoxifenbackgroundsummaryfinal.pdf (Accessed September 15, 2006).

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