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Bouffées de chaleur, tamoxifène et cytochrome P450 2D6

Hot flushes, tamoxifen and cytochrome P450 2D6

  • Synthèse / Review Article
  • Published:
Oncologie

Abstract

Cytochrome P450 2D6 (CYP2D6) is a key enzyme in the transformation of the Tamoxifen (TAM) in its most active two derivatives, a 4-hydroxy-TAM and Endoxifen. The hypothesis that a genetic polymorphism of CYP2D6 and/or concomitant absorption of these enzyme-inhibitory drugs can modify both the frequency and intensity of hot flushes and the antineoplastic therapeutic efficacy is the object of dissenting conclusions in the available literature. CYP2D6 genotyping is not the object of official recommendation at present before prescription of TAM while a common recommendation of Afssaps and INCa contraindicates the co-prescription of the paroxetine and the fluoxetine with the TAM.

Résumé

Le cytochrome P450 2D6 (CYP2D6) est un enzyme clé de la transformation du tamoxifène (TAM) en ses deux dérivés les plus actifs, le 4-hydroxy-TAM et l’endoxifène. L’hypothèse qu’un polymorphisme génétique du CYP2D6 et/ou la prise concomitante de médicaments inhibiteurs de cet enzyme puissent modifier sous TAM à la fois la fréquence et l’intensité des bouffées de chaleur (BdC) d’une part, et l’efficacité thérapeutique antinéoplasique d’autre part, fait l’objet de conclusions discordantes dans la littérature disponible. Il n’y a pas actuellement de recommandation officielle au génotypage du CYP2D6 avant prescription de TAM alors qu’une recommandation commune de l’Afssaps et de l’INCa contreindique la coprescription de la paroxétine et de la fluoxétine avec le TAM.

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Références

  1. Ahern TP, Pedersen L, Cronin-Fenton DP, et al. (2009) No increase in breast cancer recurrence with concurrent use of tamoxifen and some CYP2D6-inhibiting medications. Cancer Epidemiol Biomarkers Prev 18: OF1–OF3

    Google Scholar 

  2. Azoulay L, Dell’Aniello S, Huiart L, et al. (2011) Concurrent use of tamoxifen with CYP2D6 inhibitors and the risk of breast cancer recurrence. Breast Cancer Res Treat 126: 695–703

    Article  PubMed  CAS  Google Scholar 

  3. Borges S, Desta Z, Li L, et al. (2006) Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 80: 61–74

    Article  PubMed  CAS  Google Scholar 

  4. Boutet G (2012) Traitement des bouffées de chaleur après cancer du sein. Gynecol Obstet Fertil 40: 241–254

    Article  PubMed  CAS  Google Scholar 

  5. Brauch H, Mürdter TE, Eichelbaum M, et al. (2009) Pharmacogenomics of tamoxifen therapy. Clin Chem 55: 1770–1782

    Article  PubMed  CAS  Google Scholar 

  6. Burstein HJ, Prestrud AA, Seidenfeld J, et al. (2010) American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol 28: 3784–3796

    Article  PubMed  Google Scholar 

  7. Cuzick J, Forbes JF, Sestak I, et al. (2007) Long-term results of tamoxifen prophylaxis for breast cancer: 96-month follow-up of the randomized IBIS-I Trial. J Natl Cancer Inst 99: 272–282

    Article  PubMed  CAS  Google Scholar 

  8. Cuzick J, Sestac I, Cella D et al. (2008) Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol 12: 1143–1148

    Article  Google Scholar 

  9. Early Breast Cancer Trialists’ Collaborative group (EBCTCG) (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378: 771–784

    Google Scholar 

  10. Fisher B, Costantino JP, Wickerham DL, et al. (1998) Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 90: 1371–1388

    Article  PubMed  CAS  Google Scholar 

  11. Fleeman N, Martin-Saborido C, Payne K, et al. (2011) The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: a systematic review. Health Technol Assess 15: 1–102

    Google Scholar 

  12. Goetz MP, Rae JM, Suman VJ, et al. (2005) Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flasches. J Clin Oncol 23: 9312–9318

    Article  PubMed  CAS  Google Scholar 

  13. Goetz MP, Knox SK, Suman VJ, et al. (2007) The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 101: 113–121

    Article  PubMed  CAS  Google Scholar 

  14. Goetz MP, Schaid DJ, Wickerham D, et al. (2011) Evaluation of CYP2D6 and efficacy of tamoxifen and raloxifene in women treated for breast cancer chemoprevention: results from the NSABP P1 and P2 clinical trials. Clin Cancer Res 17: 6944–6951

    Article  PubMed  CAS  Google Scholar 

  15. Henry NL, Rae JM, Li L, et al. (2009) Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. Breast Cancer Res Treat 117: 571–575

    Article  PubMed  Google Scholar 

  16. Irvin WJ, Walko CM, Weck KE, et al. (2011) Genotype-guided tamoxifen dosing increases active metabolite exposure in women with reduced CYP2D6 metabolism: a multicenter study. J Clin Oncol 29: 3232–3239

    Article  PubMed  CAS  Google Scholar 

  17. Jin Y, Desta Z, Stearns V, et al. (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97: 30–39

    Article  PubMed  CAS  Google Scholar 

  18. Kelly CM, Juurlink DN, Gomes T, et al. (2010) Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ 340:c693

    Article  PubMed  Google Scholar 

  19. Kelly CM, Pritchard KI (2012) CYP2D6 genotype as a marker for benefit of adjuvant tamoxifen in postmenopausal women: lessons learned. J Natl Cancer Inst 104: 427–428

    Article  PubMed  CAS  Google Scholar 

  20. Lash T, Lien EA, Sorensen HT, et al. (2009) Genotype-guided tamoxifen therapy: time to pause for reflection? Lancet Oncol 10: 825–833

    Article  PubMed  CAS  Google Scholar 

  21. Loprinzi CL, Sloan J, Stearns V, et al. (2009) Newer antidepressants and Gabapentin for hot flashes: an individual patient pooled analysis. J Clin Oncol 27: 2831–2837

    Article  PubMed  CAS  Google Scholar 

  22. Madlensky L, Flatt SW, Natarajan L, et al. (2008) Hot flashes are associated with CYP2D6 genotype in breast cancer survivors taking tamoxifen. 31st Annual San Antonio Breast Cancer Symposium, San Antonio, abstract no 6045

  23. Madlensky L, Natarajan L, Tchu S, et al. (2011) Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther 89: 718–724

    Article  PubMed  CAS  Google Scholar 

  24. Mortimer JE, Flatt SW, Parker BA, et al. (2008) Tamoxifen, hot flashes and recurrence in breast cancer. Breast Cancer Rest Treat 108: 421–426

    Article  CAS  Google Scholar 

  25. Rae JM, Sikora MJ, Henry NL, et al. (2009) Cytochrome P450 2D6 activity predicts discontinuation of tamoxifen therapy in breast cancer patients. Pharmacogenomics J 9: 258–264

    Article  PubMed  CAS  Google Scholar 

  26. Rae JM (2011) Personalized tamoxifen: what is the best way forward? J Clin Oncol 29: 3206–3208

    Article  PubMed  Google Scholar 

  27. Rae JM, Drury S, Hayes DF, et al. (2012) CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst 104: 452–460

    Article  PubMed  CAS  Google Scholar 

  28. Regan MM, Leyland-Jones B, Bouzyk M, et al. (2012) CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the Breast International Group 1-98 trial. J Natl Cancer Inst 104: 441–451

    Article  PubMed  CAS  Google Scholar 

  29. Sideras K, Ingle JN, Ames MM, et al. (2010) Coprescription of tamoxifen and medications that inhibit CYP2D6. J Clin Oncol 28: 2768–2776

    Article  PubMed  CAS  Google Scholar 

  30. Singh MS, Francis PA, Michael M (2011) Tamoxifen, cytochrome P450 genes and breast cancer clinical outcomes. Breast 20: 111–118

    Article  PubMed  Google Scholar 

  31. Stearns V, Johnson MD, Rae JM, et al. (2003) Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Instit 95: 1758–1764

    Article  CAS  Google Scholar 

  32. Thompson AM, Johnson A, Quinlan P, et al. (2011) Comprehensive CYP2D6 genotype and adherence affect outcome in breast cancer patients treated with tamoxifen monotherapy. Breast Cancer Res Treat 125: 279–287

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Service de chirurgie gynécologique et médecine de la reproduction, CHU de Bordeaux, groupe hospitalier Pellegrin, place Amélie-Raba-Léon, F-33076, Bordeaux cedex, France

    G. Boutet

  2. Service gynécologie-obstétrique, groupe hospitalier de La Rochelle-Ré-Aunis, rue du Docteur-Schweitzer, F-17019, La Rochelle cedex, France

    G. Boutet

  3. Cabinet de gynécologie, 28, rue de Norvège, F-17000, La Rochelle, France

    G. Boutet

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Boutet, G. Bouffées de chaleur, tamoxifène et cytochrome P450 2D6 . Oncologie 14, 357–364 (2012). https://doi.org/10.1007/s10269-012-2170-9

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  • DOI: https://doi.org/10.1007/s10269-012-2170-9

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