Tissue distribution of 4-hydroxy-N-desmethyltamoxifen and tamoxifen-N-oxide

Breast Cancer Research and Treatment

Volumn 134, Issue 2, 2012, Pages 693-700

  Gjerde, Jennifer ^a,b   Gandini, Sara ^c   Guerrieri Gonzaga, Aliana ^c   Haugan Moi, Line L ^d   Aristarco, Valentina ^c   Mellgren, Gunnar ^a,b   De Censi, Andrea ^c,e   Lien, Ernst A ^a,b  

^a UNIVERSITY OF BERGEN   (Norway)

^b HAUKELAND UNIVERSITY HOSPITAL   (Norway)

^c EUROPEAN INSTITUTE OF ONCOLOGY   (Italy)

^d UNIVERSITY HOSPITAL OF NORTH NORWAY   (Norway)

^e GALLIERA HOSPITAL   (Italy)

Author keywords

4 OH N desmethyltamoxifen; Breast cancer; Endoxifen; MCF 7; Tamoxifen; Tamoxifen N oxide

Indexed keywords

AFIMOXIFENE; DRUG METABOLITE; ENDOXIFEN; N DESDIMETHYL TAMOXIFEN; NORTAMOXIFEN; TAMOXIFEN; TAMOXIFEN N OXIDE; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; BREAST BIOPSY; BREAST TUMOR; CELL ASSAY; CELL STRAIN MCF 7; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG DOSE INCREASE; DRUG EFFECT; DRUG MONITORING; DRUG SAFETY; DRUG TISSUE LEVEL; DRUG TOLERABILITY; FEMALE; HOT FLUSH; HUMAN; HUMAN CELL; HUMAN TISSUE; LOW DRUG DOSE; MAJOR CLINICAL STUDY; NIGHT SWEAT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIDE EFFECT; SWEATING; TISSUE DISTRIBUTION; TUMOR LOCALIZATION;

AGED; ANTINEOPLASTIC AGENTS, HORMONAL; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; FEMALE; HUMANS; MIDDLE AGED; RANDOMIZED CONTROLLED TRIALS AS TOPIC; STATISTICS, NONPARAMETRIC; TAMOXIFEN; TISSUE DISTRIBUTION;

EID: 84868205777     PISSN: 01676806     EISSN: 15737217     Source Type: Journal    
DOI: 10.1007/s10549-012-2074-9     Document Type: Article

References (45)

1. Parton M, Smith IE (2008) Controversies in the management of patients with breast cancer: adjuvant endocrine therapy in premenopausal women. J Clin Oncol Off J Am Soc Clin Oncol 26:745-752. doi:10.1200/JCO.2007.14.3016
2. Cuzick J, Powles T, Veronesi U, Forbes J, Edwards R, Ashley S, Boyle P (2003) Overview of the main outcomes in breast-cancer prevention trials. Lancet 361:296-300. doi:10.1016/S0140-6736 (03) 12342-2
3. Viale G, Regan MM, Dell'Orto P, Mastropasqua MG, Maiorano E, Rasmussen BB, MacGrogan G, Forbes JF, Paridaens RJ, Colleoni M, Lang I, Thurlimann B, Mouridsen H, Mauriac L, Gelber RD, Price KN, Goldhirsch A, Gusterson BA, Coates AS (2011) Which patients benefit most from adjuvant aromatase inhibitors? results using a composite measure of prognostic risk in the BIG 1-98 randomized trial. Ann Oncol Off J Eur Soc Med Oncol/ESMO 22:2201-2207. doi:10.1093/annonc/ mdq738
4. Amir E, Seruga B, Niraula S, Carlsson L, Ocana A (2011) Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Nat Cancer Inst 103:1299-1309. doi:10.1093/jnci/djr242
5. Borgna JL, Rochefort H (1980) High-affinity binding to the estrogen receptor of [3H]4-hydroxytamoxifen, an active antiestrogen metabolite. Mol Cell Endocrinol 20:71-85
6. Lien EA, Solheim E, Kvinnsland S, Ueland PM (1988) Identification of 4-hydroxy-N-desmethyltamoxifen as a metabolite of tamoxifen in human bile. Cancer Res 48:2304-2308
7. Gallicchio L, Lord G, Tkaczuk K, Danton M, Lewis LM, Lim CK, Flaws JA (2004) Association of tamoxifen (TAM) and TAM metabolite concentrations with self-reported side effects of TAM in women with breast cancer. Breast Cancer Res Treat 85:89-97
8. Crewe HK, Ellis SW, Lennard MS, Tucker GT (1997) Variable contribution of cytochromes P450 2D6, 2C9 and 3A4 to the 4-hydroxylation of tamoxifen by human liver microsomes. Biochem Pharmacol 53:171-178
9. Lim YC, Desta Z, Flockhart DA, Skaar TC (2005) Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifen. Cancer Chemother Pharmacol 55:471-478
10. Coller JK (2003) Oxidative metabolism of tamoxifen to Z-4-hydroxy-tamoxifen by cytochrome P450 isoforms: an appraisal of in vitro studies. Clin Exp Pharmacol Physiol 30:845-848
11. Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM (2002) 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 Metab Dispos 30:869-874
12. Desta Z, Ward BA, Soukhova NV, Flockhart DA (2004) Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther 310:1062-1075
13. Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA (2003) Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Nat Cancer Inst 95:1758-1764
14. Schroth W, Antoniadou L, Fritz P, Schwab M, Muerdter T, Zanger UM, Simon W, Eichelbaum M, Brauch H (2007) Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol 25:5187-5193
15. Wegman P, Vainikka L, Stål O (2005) Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients. Breast Cancer Res 7:284-290
16. Lash TL, Lien EA, Sorensen HT, Hamilton-Dutoit S (2009) Genotype-guided tamoxifen therapy: time to pause for reflection? Lancet Oncol 10:825-833. doi:10.1016/S1470-2045 (09) 70030-0
17. Goetz MP, Schaid DJ, Wickerham DL, Safgren S, Mushiroda T, Kubo M, Batzler A, Costantino JP, Vogel VG, Paik S, Carlson EE, Flockhart DA, Wolmark N, Nakamura Y, Weinshilboum RM, Ingle JN, Ames MM (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 Off J Am Assoc Cancer Res 17:6944-6951. doi:10.1158/1078-0432. CCR-11-0860
18. Moyer AM, Suman VJ, Weinshilboum RM, Avula R, Black JL, Safgren SL, Kuffel MJ, Ames MM, Ingle JN, Goetz MP (2011) SULT1A1, CYP2C19 and disease-free survival in early breast cancer patients receiving tamoxifen. Pharmacogenomics 12:1535-1543. doi:10.2217/pgs.11.97
19. Goetz M, Suman V (2010) 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 116:1007; author reply 1008. doi:10.1002/cncr.24827
20. Mani C, Gelboin HV, Park SS, Pearce R, Parkinson A, Kupfer D (1993) Metabolism of the antimammary cancer antiestrogenic agent tamoxifen. I. Cytochrome P-450-catalyzed N-demethylation and 4-hydroxylation. Drug Metab Dispos Biol Fate Chem 21:645-656
21. Bates DJ, Foster AB, Griggs LJ, Jarman M, Leclercq G, Devleeshouwer N (1982) Metabolism of tamoxifen by isolated rat hepatocytes: anti-estrogenic activity of tamoxifen N-oxide. Biochem Pharmacol 31:2823-2827
22. Parte P, Kupfer D (2005) Oxidation of tamoxifen by human flavin-containing monooxygenase (FMO) 1 and FMO3 to tamoxifen-N-oxide and its novel reduction back to tamoxifen by human cytochromes P450 and hemoglobin. Drug Metab Dispos 33:1446-1452
23. Krueger SK, Vandyke JE, Williams DE, Hines RN (2006) The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines. Drug Metab Rev 38:139-147
24. Decensi A, Robertson C, Viale G, Pigatto F, Johansson H, Kisanga ER, Veronesi P, Torrisi R, Cazzaniga M, Mora S, Sandri MT, Pelosi G, Luini A, Goldhirsch A, Lien EA, Veronesi U (2003) A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers. J Nat Cancer Inst 95:779-790
25. Kisanga ER, Gjerde J, Guerrieri-Gonzaga A, Pigatto F, Pesci-Feltri A, Robertson C, Serrano D, Pelosi G, Decensi A, Lien EA (2004) Tamoxifen and metabolite concentrations in serum and breast cancer tissue during three dose regimens in a randomized preoperative trial. Clin Cancer Res 10:2336-2343
26. Buckley MM, Goa KL (1989) Tamoxifen: a reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic use. Drugs 37:451-490
27. Lien EA, Solheim E, Ueland PM (1991) Distribution of tamoxifen and its metabolites in rat and human tissues during steadystate treatment. Cancer Res 51:4837-4844
28. Gjerde J, Kisanga ER, Hauglid M, Holm PI, Mellgren G, Lien EA (2005) Identification and quantification of tamoxifen and four metabolites in serum by liquid chromatography-tandem mass spectrometry. J Chromatogr A 1082:6-14
29. Gjerde J, Hauglid M, Breilid H, Lundgren S, Varhaug JE, Kisanga ER, Mellgren G, Steen VM, Lien EA (2008) Effects of CYP2D6 and SULT1A1 genotypes including SULT1A1 gene copy number on tamoxifen metabolism. Ann Oncol 19:56-61
30. Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E (1996) A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas 24:161-175
31. Lien EA, Anker G, Ueland PM (1995) Pharmacokinetics of tamoxifen in premenopausal and postmenopausal women with breast cancer. J Steroid Biochem Mol Biol 55:229-231
32. Peyrade F, Frenay M, Etienne MC, Ruch F, Guillemare C, Francois E, Namer M, Ferrero JM, Milano G (1996) Age-related difference in tamoxifen disposition. Clin Pharmacol Ther 59:401-410. doi:10.1016/S0009-9236 (96) 90108-3
33. Sheth HR, Lord G, Tkaczuk K, Danton M, Lewis LM, Langenberg P, Lim CK, Flaws JA (2003) Aging may be associated with concentrations of tamoxifen and its metabolites in breast cancer patients. J Womens Health (Larchmt) 12:799-808
34. Floren LC, Hebert MF, Venook AP, Jordan VC, Cisneros A, Somberg KA (1998) Tamoxifen in liver disease: potential exacerbation of hepatic dysfunction. Ann Oncol 9:1123-1126
35. Gjerde J, Geisler J, Lundgren S, Ekse D, Varhaug JE, Mellgren G, Steen VM, Lien EA (2010) Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer. BMC Cancer 10:313. doi:10.1186/1471-2407-10-313
36. Madlensky L, Natarajan L, Tchu S, Pu M, Mortimer J, Flatt SW, Nikoloff DM, Hillman G, Fontecha MR, Lawrence HJ, Parker BA, Wu AH, Pierce JP (2011) Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther 89:718-725. doi:10.1038/clpt.2011.32
37. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Nat Cancer Inst 90:1371-1388
38. Carter SJ, Li XF, Mackey JR, Modi S, Hanson J, Dovichi NJ (2001) Biomonitoring of urinary tamoxifen and its metabolites from breast cancer patients using nonaqueous capillary electrophoresis with electrospray mass spectrometry. Electrophoresis 22:2730-2736
39. Lu WJ, Desta Z, Flockhart DA (2012) Tamoxifen metabolites as active inhibitors of aromatase in the treatment of breast cancer. Breast Cancer Res Treat 131:473-481. doi:10.1007/s10549-011-1428-z
40. Demissie S, Silliman RA, Lash TL (2001) Adjuvant tamoxifen: predictors of use, side effects, and discontinuation in older women. J Clin Oncol 19:322-328
41. Chlebowski RT, Geller ML (2006) Adherence to endocrine therapy for breast cancer. Oncology 71:1-9
42. Ma AM, Barone J, Wallis AE, Wu NJ, Garcia LB, Estabrook A, Rosenbaum-Smith SM, Tartter PI (2008) Noncompliance with adjuvant radiation, chemotherapy, or hormonal therapy in breast cancer patients. Am J Surg 196:500-504. doi:10.1016/j.amjsurg.2008.06.027
43. McCowan C, Shearer J, Donnan PT, Dewar JA, Crilly M, Thompson AM, Fahey TP (2008) Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer. Br J Cancer 99:1763-1768. doi:10.1038/sj.bjc.6604758
44. Bouchardy C, Rapiti E, Fioretta G, Laissue P, Neyroud-Caspar I, Schafer P, Kurtz J, Sappino AP, Vlastos G (2003) Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol 21:3580-3587. doi:10.1200/JCO.2003.02.046 JCO.2003.02.046
45. Teunissen SF, Jager NG, Rosing H, Schinkel AH, Schellens JH, Beijnen JH (2011) Development and validation of a quantitative assay for the determination of tamoxifen and its five main phase I metabolites in human serum using liquid chromatography coupled with tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 879:1677-1685. doi:10.1016/j.jchromb.2011.04.011