Should CYP2D6 inhibitors be administered in conjunction with tamoxifen?

Expert Review of Anticancer Therapy

Volumn 11, Issue 2, 2011, Pages 185-193

  Zembutsu, Hitoshi ^a   Sasa, Mitsunori ^b   Kiyotani, Kazuma ^c   Mushiroda, Taisei ^c   Nakamura, Yusuke ^a  

^a UNIVERSITY OF TOKYO   (Japan)

^b Tokushima Breast Care Clinic   (Japan)

^c RIKEN   (Japan)

Author keywords

chemoprevention; CYP2D6; CYP2D6 inhibitor; endoxifen; genotype; prophylactic mastectomy; tamoxifen

Indexed keywords

AFIMOXIFENE; AMFEBUTAMONE; CITALOPRAM; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A; DESVENLAFAXINE; DRUG METABOLITE; DULOXETINE; ESCITALOPRAM; FLUOXETINE; FLUVOXAMINE; GLUCURONOSYLTRANSFERASE; MIRTAZAPINE; PAROXETINE; REBOXETINE; SERTRALINE; SULFOTRANSFERASE; TAMOXIFEN; VENLAFAXINE;

ADJUVANT THERAPY; ALLELE; BREAST CANCER; CANCER PREVENTION; CANCER RADIOTHERAPY; CANCER RISK; DISEASE FREE SURVIVAL; DRUG EFFICACY; DRUG INHIBITION; DRUG POTENCY; DRUG TRANSFORMATION; ENZYME ACTIVITY; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; MASTECTOMY; OVERALL SURVIVAL; REVIEW; TREATMENT RESPONSE;

ANTINEOPLASTIC AGENTS, HORMONAL; BREAST NEOPLASMS; CHEMOTHERAPY, ADJUVANT; CYTOCHROME P-450 CYP2D6; FEMALE; HUMANS; NEOPLASMS, HORMONE-DEPENDENT; PAROXETINE; POLYMORPHISM, GENETIC; RECEPTORS, ESTROGEN; SEROTONIN UPTAKE INHIBITORS; TAMOXIFEN; TREATMENT OUTCOME;

EID: 79952161683     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/era.10.228     Document Type: Review

References (54)

1. Blaha P, Dubsky P, Fitzal F et al. Breast cancer chemoprevention - a vision not yet realized. Eur. J. Cancer Care 18(5), 438-446 (2009).
2. Nelson HD, Fu R, Humphrey L, Smith MEB, Griffin JC, Nygren P. Comparative effectiveness of medications to reduce risk of primary breast cancer in women. Agency for Healthcare Research and Quality. 09-EHC028-EF (2009).
3. Freedman AN, Graubard BI, Rao SR, McCaskill-Stevens W, Ballard-Barbash R, Gail MH. Estimates of the number of US women who could benefit from tamoxifen for breast cancer chemoprevention. J. Natl Cancer Inst. 95(7), 526-532 (2003).
4. Vogel VG, Costantino JP, Wickerham DL et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 295(23), 2727-2741 (2006).
5. Kaplan CP, Haas JS, Perez-Stable EJ et al. Breast cancer risk reduction options: awareness, discussion, and use among women from four ethnic groups. Cancer Epidemiol. Biomarkers Prev. 15(1), 162-166 (2006).
6. Armstrong K, Quistberg DA, Micco E, Domchek S, Guerra C. Prescription of tamoxifen for breast cancer prevention by primary care physicians. Arch. Intern. Med. 166(20), 2260-2265 (2006).
7. Visvanathan K, Chlebowski RT, Hurley P et al. American society of clinical oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J. Clin. Oncol. 27(19), 3235-3258 (2009).
8. Hartmann LC, Schaid DJ, Woods JE et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N. Engl. J. Med. 340(2), 77-84 (1999).
9. Rebbeck TR, Friebel T, Lynch HT et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J. Clin. Oncol. 22(6), 1055-1062 (2004).
10. Lostumbo L, Carbine N, Wallace J, Ezzo J. Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database Syst. Rev. 4, CD002748 (2004).
11. Bevers TB, Anderson BO, Bonaccio E et al. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis. J. Natl Compr. Canc. Network 7(10), 1060-1096 (2009).
12. McLaughlin CC, Lillquist PP, Edge SB. Surveillance of prophylactic mastectomy: trends in use from 1995 through 2005. Cancer 115(23), 5404-5412 (2009).
13. Ingle JN, Suman VJ, Johnson PA et al. Evaluation of tamoxifen plus letrozole with assessment of pharmacokinetic interaction in postmenopausal women with metastatic breast cancer. Clin. Cancer Res. 5(7), 1642-1649 (1999).
14. Stearns V, Johnson MD, Rae JM et al. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J. Natl Cancer Inst. 95(23), 1758-1764 (2003).
15. Jin Y, Desta Z, Stearns V et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J. Natl Cancer Inst. 97(1), 30-39 (2005).
16. Clarke R, Liu MC, Bouker KB et al. Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene 22(47), 7316-7339 (2003).
17. Jaremko M, Kasai Y, Barginear MF et al. Tamoxifen metabolite isomer separation and quantification by liquid chromatography-tandem mass spectrometry. Anal. Chem. 82(24), 10186-10193 (2010).
18. Lien EA, Solheim E, Kvinnsland S, Ueland PM. Identification of 4-hydroxy-N-desmethyltamoxifen as a metabolite of tamoxifen in human bile. Cancer Res. 48(8), 2304-2308 (1988).
19. 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. 80(1), 61-74 (2006).
20. Desta Z, Ward BA, Soukhova NV, Flockhart DA. Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J. Pharmacol. Exp. Ther. 310(3), 1062-1075 (2004).
21. Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J. 5(1), 6-13 (2005).
22. Gross AS, Kroemer HK, Eichelbaum M. Genetic polymorphism of drug metabolism in humans. Adv. Exp. Med. Biol. 283, 627-640 (1991).
23. Sistonen J, Sajantila A, Lao O, Corander J, Barbujani G, Fuselli S. CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenet. Genomics 17(2), 93-101 (2007).
24. Sideras K, Ingle JN, Ames MM et al. Coprescription of tamoxifen and medications that inhibit CYP2D6. J. Clin. Oncol. 28(16), 2768-2776 (2010). Well-balanced review article that presents the issues of coprescription of tamoxifen and CYP2D6 inhibitors.
25. Zanger UM, Raimundo S, Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn. Schmiedebergs. Arch. Pharmacol. 369(1), 23-37 (2004).
26. Wu X, Hawse JR, Subramaniam M, Goetz MP, Ingle JN, Spelsberg TC. The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells. Cancer Res. 69(5), 1722-1727 (2009).
27. Lim HS, Ju Lee H, Seok Lee K, Sook Lee E, Jang IJ, Ro J. Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer. J. Clin. Oncol. 25(25), 3837-3845 (2007).
28. Kiyotani K, Mushiroda T, Imamura CK et al. Significant effect of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients. J. Clin. Oncol. 28(8), 1287-1293 (2010).
29. Goetz MP, Rae JM, Suman VJ et al. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J. Clin. Oncol. 23(36), 9312-9318 (2005).
30. Goetz MP, Knox SK, Suman VJ et al. The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res. Treat. 101(1), 113-121 (2007).
31. 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. 25(33), 5187-5193 (2007).
32. Schroth W, Goetz MP, Hamann U et al. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 302(13), 1429-1436 (2009).
33. Kiyotani K, Mushiroda T, Sasa M et al. Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy. Cancer Sci. 99(5), 995-999 (2008).
34. Nowell SA, Ahn J, Rae JM 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. 91(3), 249-258 (2005).
35. Wegman P, Elingarami S, Carstensen J, Stal O, Nordenskjold B, Wingren S. Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Breast Cancer Res. 9(1), R7 (2007).
36. Wegman P, Vainikka L, Stal O et al. Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients. Breast Cancer Res. 7(3), 284-290 (2005).
37. Xu Y, Sun Y, Yao L et al. Association between CYP2D6*10 genotype and survival of breast cancer patients receiving tamoxifen treatment. Ann. Oncol. 19(8), 1423-1429 (2008).
38. Ramon y Cajal T, Altes A, Pare L et al. Impact of CYP2D6 polymorphisms in tamoxifen adjuvant breast cancer treatment. Breast Cancer Res. Treat. 119(1), 33-38 (2009).
39. Bijl MJ, van Schaik RH, Lammers LA et al. The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users. Breast Cancer Res. Treat. 118(1), 125-130 (2009).
40. Newman WG, Hadfield KD, Latif A et al. Impaired tamoxifen metabolism reduces survival in familial breast cancer patients. Clin. Cancer Res. 14(18), 5913-5918 (2008).
41. Hoskins JM, Carey LA, McLeod HL. CYP2D6 and tamoxifen: DNA matters in breast cancer. Nat. Rev. Cancer 9(8), 576-586 (2009).
42. Lash TL, Rosenberg CL. Evidence and practice regarding the role for CYP2D6 inhibition in decisions about tamoxifen therapy. J. Clin. Oncol. 28(8), 1273-1275 (2010).
43. Kiyotani K, Mushiroda T, Hosono N et al. Lessons for pharmacogenomics studies: association study between CYP2D6 genotype and tamoxifen response. Pharmacogenet. Genomics 20(9), 565-568 (2010).
44. Ahern TP, Pedersen L, Cronin-Fenton DP, Sorensen HT, Lash TL. No increase in breast cancer recurrence with concurrent use of tamoxifen and some CYP2D6-inhibiting medications. Cancer Epidemiol. Biomarkers Prev. 18(9), 2562-2564 (2009).
45. Kelly CM, Juurlink DN, Gomes T et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. Br. Med. J. 340, c693 (2010).
46. Azoulay L, Dell'aniello S, Huiart L, du Fort GG, Suissa S. Concurrent use of tamoxifen with CYP2D6 inhibitors and the risk of breast cancer recurrence. Breast Cancer Res. Treat. DOI: 10.1007/s10549-010-1162-y (2010) (Epub ahead of print).
47. Siegelmann-Danieli N, Kurnik D, Lomnicky Y et al. Potent CYP2D6 inhibiting drugs do not increase relapse rate in early breast cancer patients treated with adjuvant tamoxifen. Breast Cancer Res. Treat. 125(2), 505-510 (2010).
48. Desmarais JE, Looper KJ. Managing menopausal symptoms and depression in tamoxifen users: implications of drug and medicinal interactions. Maturitas 67(4), 296-308 (2010).
49. Dezentjé VO, van Blijderveen NJ, Gelderblom H et al. Effect of concomitant CYP2D6 inhibitor use and tamoxifen adherence on breast cancer recurrence in early-stage breast cancer. J. Clin. Oncol. 28(14), 2423-2429 (2010).
50. Ferraldeschi R, Howell SJ, Thompson AM et al. Avoidance of CYP2D6 inhibitors in patients receiving tamoxifen. J. Clin. Oncol. 28(29), e584-e585 (2010).
51. Okishiro M, Taguchi T, Jin Kim S, Shimazu K, Tamaki Y, Noguchi S. 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 115(5), 952-961 (2009).
52. NCCN: Updated NCCN guidelines for breast cancer discourages prophylactic mastectomy in women other than those at high risk www.nccn.org/about/news/ newsinfo.asp?NewsID=226
53. CYP2D6 allele nomenclature www.cypalleles.ki.se/cyp2d6.htm
54. US FDA: Drug development and drug interactions: table of substrates, inhibitors and inducers www.fda.gov/Drugs/DevelopmentApprovalProcess/ DevelopmentResources/DrugInteractionsLabeling/ucm081177.htm#classInhibit