Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

References

• Torre LA, Siegel RL, Ward EM, et al. Global cancer incidence and mortality rates and trends–an update. Cancer Epidemiol Biomarkers Prev. 2016;25(1):16–27.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Breast cancer. [online]; 2019. [cited 2018 Nov 30]. Available from: https://www.who.int/cancer/prevention/diagnosis-screening/breast-cancer/en/
   Google Scholar
• Huang B, Warner M, Gustafsson JA. Estrogen receptors in breast carcinogenesis and endocrine therapy. Mol Cell Endocrinol. 2015;418(Pt 3):240–244.
   PubMedGoogle Scholar
• Klein DJ, Thorn CF, Desta Z, et al. PharmGKB summary: tamoxifen pathway, pharmacokinetics. Pharmacogenet Genomics. 2013;23(11):643–647.
   PubMed Web of Science ®Google Scholar
• Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. J Clin Oncol. 2014;32(21):2255–2269.
   PubMed Web of Science ®Google Scholar
• Rugo HS, Rumble RB, Macrae E, et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American society of clinical oncology guideline. J Clin Oncol. 2016;34(25):3069–3103.
   PubMed Web of Science ®Google Scholar
• Senkus E, Kyriakides S, Ohno S, et al. Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v8–v30.
   PubMed Web of Science ®Google Scholar
• Early Breast Cancer Trialists‘ Collaborative G. 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(9472):1687–1717.
   PubMed Web of Science ®Google Scholar
• Early Breast Cancer Trialists‘ Collaborative G. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001):1341–1352.
   PubMed Web of Science ®Google Scholar
• Davies C, Godwin J, Gray R, et al. 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(9793):771–784.
   PubMed Web of Science ®Google Scholar
• Cuzick J, Sestak I, Baum M, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010;11(12):1135–1141.
   PubMed Web of Science ®Google Scholar
• Thurlimann B, Robertson JF, Nabholtz JM, et al. Efficacy of tamoxifen following anastrozole (‘Arimidex‘) compared with anastrozole following tamoxifen as first-line treatment for advanced breast cancer in postmenopausal women. Eur J Cancer. 2003;39(16):2310–2317.
   PubMed Web of Science ®Google Scholar
• Lien EA, Soiland H, Lundgren S, et al. Serum concentrations of tamoxifen and its metabolites increase with age during steady-state treatment. Breast Cancer Res Treat. 2013;141(2):243–248.
   PubMed Web of Science ®Google Scholar
• Lenehan JG, Teft WA, Kim RB. Comparison of endoxifen levels between male and female breast cancer patients treated with tamoxifen. J clin oncol. 2016;34:578. Conference.
   Web of Science ®Google Scholar
• Brauch H, Murdter TE, Eichelbaum M, et al. Pharmacogenomics of tamoxifen therapy. Clin Chem. 2009;55(10):1770–1782.
   PubMed Web of Science ®Google Scholar
• Goetz MP, Kamal A, Ames MM. Tamoxifen pharmacogenomics: the role of CYP2D6 as a predictor of drug response. Clin Pharmacol Ther. 2008;83(1):160–166.
   PubMed Web of Science ®Google Scholar
• Brauch H, Schwab M. Prediction of tamoxifen outcome by genetic variation of CYP2D6 in post-menopausal women with early breast cancer. Br J Clin Pharmacol. 2014;77(4):695–703.
   PubMed Web of Science ®Google Scholar
• Knox SK, Ingle JN, Suman VJ, et al. Cytochrome P450 2D6 status predicts breast cancer relapse in women receiving adjuvant tamoxifen (Tam). J clin oncol. 2006;24(18):4S–4S.
   PubMed Web of Science ®Google Scholar
• Saladores P, Murdter T, Eccles D, et al. Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Pharmacogenomics J. 2015;15(1):84–94.
   PubMed Web of Science ®Google Scholar
• 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. 2009;302(13):1429–1436.
   PubMed Web of Science ®Google Scholar
• Sanchez-Spitman A, Dezentje V, Swen J, et al. Tamoxifen pharmacogenetics and metabolism: results from the prospective CYPTAM study. J Clin Oncol. 2019;37(8):636–646.
   PubMed Web of Science ®Google Scholar
• de Vries Schultink AHM, Huitema ADR, Beijnen JH. Therapeutic drug monitoring of endoxifen as an alternative for CYP2D6 genotyping in individualizing tamoxifen therapy. Breast. 2018;42:38–40.
   PubMed Web of Science ®Google Scholar
• Goetz MP, Suman VJ, Reid JM, et al. First-in-human phase i study of the tamoxifen metabolite Z-Endoxifen in women with endocrine-refractory metastatic breast cancer. J Clin Oncol. 2017;35(30):3391–3400.
   PubMed Web of Science ®Google Scholar
• Lien EA, Solheim E, Lea OA, et al. Distribution of 4-hydroxy-N-desmethyltamoxifen and other tamoxifen metabolites in human biological fluids during tamoxifen treatment. Cancer Res. 1989;49(8):2175–2183.
   PubMed Web of Science ®Google Scholar
• 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. 2003;95(23):1758–1764.
   PubMed Web of Science ®Google Scholar
• Lu WJ, 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(1):99–109.
   PubMed Web of Science ®Google Scholar
• Lim JS, Sutiman N, Muerdter TE, 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(6):1142–1152.
   PubMed Web of Science ®Google Scholar
• Lv W, 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(11):4611–4618.
   PubMed Web of Science ®Google Scholar
• Ma J, Chu Z, Lu JBL, et al. The cytochrome P450 enzyme responsible for the production of (Z)-norendoxifen in vitro. Chem Biodivers. 2018;15(1).
   Google Scholar
• Murdter TE, 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):708–717.
   PubMed Web of Science ®Google Scholar
• Brauch H, Schroth W, Goetz MP, et al. Tamoxifen use in postmenopausal breast cancer: CYP2D6 matters. J Clin Oncol. 2013;31(2):176–180.
   PubMed Web of Science ®Google Scholar
• Schroth W, Winter S, Murdter T, et al. Improved prediction of endoxifen metabolism by CYP2D6 genotype in breast cancer patients treated with tamoxifen. Front Pharmacol. 2017;8:582.
   PubMed Web of Science ®Google Scholar
• Pharmvar.org. (2019). PharmVar [online]. Available at: https://www.pharmvar.org/gene/CYP2D6 [Accessed 28 Apr, 2019].
   Google Scholar
• Sachse C, Brockmoller J, Bauer S, et al. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet. 1997;60(2):284–295.
   PubMed Web of Science ®Google Scholar
• Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002;3(2):229–243.
   PubMed Web of Science ®Google Scholar
• Masimirembwa CM, Hasler JA. Genetic polymorphism of drug metabolising enzymes in African populations: implications for the use of neuroleptics and antidepressants. Brain Res Bull. 1997;44(5):561–571.
   PubMed Web of Science ®Google Scholar
• Goetz MP, Sangkuhl K, Guchelaar HJ, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy. Clin Pharmacol Ther. 2018;103(5):770–777.
   PubMed Web of Science ®Google Scholar
• 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. 2005;23(36):9312–9318.
   PubMed Web of Science ®Google Scholar
• Province MA, Goetz MP, Brauch H, et al. CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations. Clin Pharmacol Ther. 2014;95(2):216–227.
   PubMed Web of Science ®Google Scholar
• Rae JM, Drury S, Hayes DF, et al. CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst. 2012;104(6):452–460.
   PubMed Web of Science ®Google Scholar
• Regan MM, 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):441–451.
   PubMed Web of Science ®Google Scholar
• Dezentje VO, van Schaik RH, Vletter-Bogaartz JM, et al. CYP2D6 genotype in relation to tamoxifen efficacy in a Dutch cohort of the tamoxifen exemestane adjuvant multinational (TEAM) trial. Breast Cancer Res Treat. 2013;140(2):363–373.
   PubMed Web of Science ®Google Scholar
• Stanton V Jr. Re: 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):1265–1266. author reply 1266-1268.
   PubMedGoogle Scholar
• Pharoah PD, Abraham J, Caldas C. Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial and Re: CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst. 2012;104(16):1263–1264. author reply 1266-1268.
   PubMedGoogle Scholar
• Nakamura Y, Ratain MJ, Cox NJ, et al. Re: 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. author reply 1266-1268.
   PubMedGoogle Scholar
• Goetz MP, Sun JX, Suman VJ, et al. Loss of heterozygosity at the CYP2D6 locus in breast cancer: implications for germline pharmacogenetic studies. J Natl Cancer Inst. 2014 Dec 8;107(2). doi:10.1093/jnci/dju401
   PubMedGoogle Scholar
• Sanchez-Spitman A, Dezentje V, Swen J, et al. Tamoxifen pharmacogenetics and metabolism: results from the prospective CYPTAM study. J Clin Oncol. 2019;37(8):636–646.
   PubMed Web of Science ®Google Scholar
• Accessdata.fda.gov. (2019). Drug Approval Package: Nolvadex (Tamoxifen Citrate) NDA #21-109 [online]. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21109_Nolvadex.cfm [Accessed 28 Apr, 2019].
   Google Scholar
• Romero-Lorca A, Novillo A, Gaibar M, et al. Impacts of the glucuronidase genotypes UGT1A4, UGT2B7, UGT2B15 and UGT2B17 on tamoxifen metabolism in breast cancer patients. PLoS One. 2015;10(7):e0132269.
   PubMed Web of Science ®Google Scholar
• Sun D, Chen G, Dellinger RW, et al. Characterization of tamoxifen and 4-hydroxytamoxifen glucuronidation by human UGT1A4 variants. Breast Cancer Res. 2006;8(4):R50.
   PubMed Web of Science ®Google Scholar
• Parte P, Kupfer D. 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. 2005;33(10):1446–1452.
   PubMed Web of Science ®Google Scholar
• Krueger SK, Vandyke JE, Williams DE, et al. The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines. Drug Metab Rev. 2006;38(1–2):139–147.
   PubMed Web of Science ®Google Scholar
• Gjerde J, Gandini S, Guerrieri-Gonzaga A, et al. Tissue distribution of 4-hydroxy-N-desmethyltamoxifen and tamoxifen-N-oxide. Breast Cancer Res Treat. 2012;134(2):693–700.
   PubMed Web of Science ®Google Scholar
• Kim SY, Suzuki N, Laxmi YR, et al. Genotoxic mechanism of tamoxifen in developing endometrial cancer. Drug Metab Rev. 2004;36(2):199–218.
   PubMed Web of Science ®Google Scholar
• Dahmane E, Mercier T, Zanolari B, et al. An ultra performance liquid chromatography-tandem MS assay for tamoxifen metabolites profiling in plasma: first evidence of 4‘-hydroxylated metabolites in breast cancer patients. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878(32):3402–3414.
   PubMed Web of Science ®Google Scholar
• Crewe HK, Notley LM, Wunsch RM, et al. Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4‘-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002;30(8):869–874.
   PubMed Web of Science ®Google Scholar
• Cuevas ME, Lindeman TE. In vitro cytotoxicity of 4‘-OH-tamoxifen and estradiol in human endometrial adenocarcinoma cells HEC-1A and HEC-1B. Oncol Rep. 2015;33(1):464–470.
   PubMed Web of Science ®Google Scholar
• Mugundu GM, Sallans L, Guo Y, et al. Assessment of the impact of CYP3A polymorphisms on the formation of alpha-hydroxytamoxifen and N-desmethyltamoxifen in human liver microsomes. Drug Metab Dispos. 2012;40(2):389–396.
   PubMed Web of Science ®Google Scholar
• Notley LM, Crewe KH, Taylor PJ, et al. Characterization of the human cytochrome P450 forms involved in metabolism of tamoxifen to its alpha-hydroxy and alpha,4-dihydroxy derivatives. Chem Res Toxicol. 2005;18(10):1611–1618.
   PubMed Web of Science ®Google Scholar
• Sutiman N, Lim JS, Muerdter TE, et al. Pharmacogenetics of UGT1A4, UGT2B7 and UGT2B15 and their influence on tamoxifen disposition in Asian breast cancer patients. Clin Pharmacokinet. 2016;55(10):1239–1250.
   PubMed Web of Science ®Google Scholar
• Nowell S, Sweeney C, Winters M, et al. Association between sulfotransferase 1A1 genotype and survival of breast cancer patients receiving tamoxifen therapy. J Natl Cancer Inst. 2002;94(21):1635–1640.
   PubMedGoogle Scholar
• 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. 2005;91(3):249–258.
   PubMed Web of Science ®Google Scholar
• 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. 2005;7(3):R284–R290.
   PubMed Web of Science ®Google Scholar
• Moyer AM, Suman VJ, Weinshilboum RM, et al. SULT1A1, CYP2C19 and disease-free survival in early breast cancer patients receiving tamoxifen. Pharmacogenomics. 2011;12(11):1535–1543.
   PubMed Web of Science ®Google Scholar
• 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):R7.
   PubMed Web of Science ®Google Scholar
• 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):30–39.
   PubMed Web of Science ®Google Scholar
• Gjerde J, Hauglid M, Breilid H, et al. Effects of CYP2D6 and SULT1A1 genotypes including SULT1A1 gene copy number on tamoxifen metabolism. Ann Oncol. 2008;19(1):56–61.
   PubMed Web of Science ®Google Scholar
• Fernandez-Santander A, Gaibar M, Novillo A, et al. Relationship between genotypes Sult1a2 and Cyp2d6 and tamoxifen metabolism in breast cancer patients. PLoS One. 2013;8(7):e70183.
   PubMed Web of Science ®Google Scholar
• Blevins-Primeau AS, Sun D, Chen G, et al. Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009;69(5):1892–1900.
   PubMed Web of Science ®Google Scholar
• Mizuma T. Intestinal glucuronidation metabolism may have a greater impact on oral bioavailability than hepatic glucuronidation metabolism in humans: a study with raloxifene, substrate for UGT1A1, 1A8, 1A9, and 1A10. Int J Pharm. 2009;378(1–2):140–141.
   PubMed Web of Science ®Google Scholar
• Ahern TP, Christensen M, Cronin-Fenton DP, et al. Functional polymorphisms in UDP-glucuronosyl transferases and recurrence in tamoxifen-treated breast cancer survivors. Cancer Epidemiol Biomarkers Prev. 2011;20(9):1937–1943.
   PubMed Web of Science ®Google Scholar
• Areepium N, Panomvana D, Rungwanonchai P, et al. Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients. Breast Cancer (Dove Med Press). 2013;5:73–78.
   PubMedGoogle Scholar
• Sutiman N, Lim JSL, Muerdter TE, et al. Pharmacogenetics of UGT1A4, UGT2B7 and UGT2B15 and their influence on tamoxifen disposition in Asian breast cancer patients. Clin Pharmacokinet. 2016;55(10):1239–1250.
   PubMed Web of Science ®Google Scholar
• Sahebkar A, Serban MC, Penson P, et al. The effects of tamoxifen on plasma lipoprotein(a) concentrations: systematic review and meta-analysis. Drugs. 2017;77(11):1187–1197.
   PubMed Web of Science ®Google Scholar
• Wu AH, Pike MC, Williams LD, et al. Tamoxifen, soy, and lifestyle factors in Asian American women with breast cancer. J Clin Oncol. 2007;25(21):3024–3030.
   PubMed Web of Science ®Google Scholar
• Peyrade F, Frenay M, Etienne MC, et al. Age-related difference in tamoxifen disposition. Clin Pharmacol Ther. 1996;59(4):401–410.
   PubMed Web of Science ®Google Scholar
• Antunes MV, Timm TA, de Oliveira V, et al. Influence of CYP2D6 and CYP3A4 phenotypes, drug interactions, and vitamin D status on tamoxifen biotransformation. Ther Drug Monit. 2015;37(6):733–744.
   PubMed Web of Science ®Google Scholar
• Davis SR, Lambrinoudaki I, Lumsden M, et al. Menopause. Nat Rev Dis Primers. 2015;1:15004.
   PubMed Web of Science ®Google Scholar
• Tan JL, Eastment JG, Poudel A, et al. Age-related changes in hepatic function: an update on implications for drug therapy. Drugs Aging. 2015;32(12):999–1008.
   PubMed Web of Science ®Google Scholar
• Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57–65.
   PubMed Web of Science ®Google Scholar
• Piccirillo JF, Vlahiotis A, Barrett LB, et al. The changing prevalence of comorbidity across the age spectrum. Crit Rev Oncol Hematol. 2008;67(2):124–132.
   PubMed Web of Science ®Google Scholar
• Madlensky L, Natarajan L, Tchu S, et al. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther. 2011;89(5):718–725.
   PubMed Web of Science ®Google Scholar
• Antunes MV, de Oliveira V, Raymundo S, et al. CYP3A4*22 is related to increased plasma levels of 4-hydroxytamoxifen and partially compensates for reduced CYP2D6 activation of tamoxifen. Pharmacogenomics. 2015;16(6):601–617.
   PubMed Web of Science ®Google Scholar
• Sendur MA, Aksoy S, Ozdemir NY, et al. Effect of body mass index on the efficacy of adjuvant tamoxifen in premenopausal patients with hormone receptor-positive breast cancer. J BUON. 2016;21(1):27–34.
   PubMed Web of Science ®Google Scholar
• Goodwin PJ, Pritchard KI. Obesity and hormone therapy in breast cancer: an unfinished puzzle. J Clin Oncol. 2010;28(21):3405–3407.
   PubMed Web of Science ®Google Scholar
• Singh BN, Malhotra BK. Effects of food on the clinical pharmacokinetics of anticancer agents: underlying mechanisms and implications for oral chemotherapy. Clin Pharmacokinet. 2004;43(15):1127–1156.
   PubMed Web of Science ®Google Scholar
• Binkhorst L, Kloth JSL, de Wit AS, et al. Circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients. Breast Cancer Res Treat. 2015;152(1):119–128.
   PubMed Web of Science ®Google Scholar
• Teft WA, Gong IY, Dingle B, et al. CYP3A4 and seasonal variation in vitamin D status in addition to CYP2D6 contribute to therapeutic endoxifen level during tamoxifen therapy. Breast Cancer Res Treat. 2013;139(1):95–105.
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177–193.
   PubMed Web of Science ®Google Scholar
• Eggemann H, Ignatov A, Smith BJ, et al. Adjuvant therapy with tamoxifen compared to aromatase inhibitors for 257 male breast cancer patients. Breast Cancer Res Treat. 2013;137(2):465–470.
   PubMed Web of Science ®Google Scholar
• Lenehan JG, Teft WA, Kim RB. Comparison of endoxifen levels between male and female breast cancer patients treated with tamoxifen. J Clin Oncol. 2016;34(15_suppl):578–578.
   Web of Science ®Google Scholar
• Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2009;48(3):143–157.
   PubMed Web of Science ®Google Scholar
• Catsburg C, Kirsh VA, Soskolne CL, et al. Active cigarette smoking and the risk of breast cancer: a cohort study. Cancer Epidemiol. 2014;38(4):376–381.
   PubMed Web of Science ®Google Scholar
• Catsburg C, Miller AB, Rohan TE. Active cigarette smoking and risk of breast cancer. Int J Cancer. 2015;136(9):2204–2209.
   PubMed Web of Science ®Google Scholar
• Persson M, Simonsson M, Markkula A, et al. Impacts of smoking on endocrine treatment response in a prospective breast cancer cohort. Br J Cancer. 2016;115(3):382–390.
   PubMed Web of Science ®Google Scholar
• Zhan M, Flaws JA, Gallicchio L, et al. Profiles of tamoxifen-related side effects by race and smoking status in women with breast cancer. Cancer Detect Prev. 2007;31(5):384–390.
   PubMedGoogle Scholar
• Imperato F, Marziani R, Perniola G, et al. Effects of tamoxifen and estrogen replacement therapy on lipid metabolism and some other cardiovascular risk factors. A prospective study in hysterectomised women. Minerva Ginecol. 2003;55(1):87–93.
   PubMedGoogle Scholar
• Nordenskjold B, Rosell J, Rutqvist LE, et al. Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy: results from a randomized trial. J Natl Cancer Inst. 2005;97(21):1609–1610.
   PubMedGoogle Scholar
• Clarke SC, Schofield PM, Grace AA, et al. Tamoxifen effects on endothelial function and cardiovascular risk factors in men with advanced atherosclerosis. Circulation. 2001;103(11):1497–1502.
   PubMed Web of Science ®Google Scholar
• Shewmon DA, Stock JL, Rosen CJ, et al. Tamoxifen and estrogen lower circulating lipoprotein(a) concentrations in healthy postmenopausal women. Arterioscler Thromb. 1994;14(10):1586–1593.
   PubMedGoogle Scholar
• Zainal NZ, Nik-Jaafar NR, Baharudin A, et al. Prevalence of depression in breast cancer survivors: a systematic review of observational studies. Asian Pac J Cancer Prev. 2013;14(4):2649–2656.
   PubMedGoogle Scholar
• Pirl WF. Evidence report on the occurrence, assessment, and treatment of depression in cancer patients. J Natl Cancer Inst Monogr. 2004;32:32–39.
   PubMedGoogle Scholar
• Jeppesen U, Gram LF, 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):73–78.
   PubMed Web of Science ®Google Scholar
• 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(1):61–74.
   PubMed Web of Science ®Google Scholar
• Dusetzina SB, Alexander GC, Freedman RA, et al. Trends in co-prescribing of antidepressants and tamoxifen among women with breast cancer, 2004–2010. Breast Cancer Res Treat. 2013;137(1):285–296.
   PubMed Web of Science ®Google Scholar
• Dieudonne AS, De Nys K, Casteels M, et al. How often did Belgian physicians co-prescribe tamoxifen with strong CYP2D6 inhibitors over the last 6 years? Acta Clin Belg. 2014;69(1):47–52.
   PubMed Web of Science ®Google Scholar
• Binkhorst L, Mathijssen RH, van Herk-Sukel MP, et al. Unjustified prescribing of CYP2D6 inhibiting SSRIs in women treated with tamoxifen. Breast Cancer Res Treat. 2013;139(3):923–929.
   PubMed Web of Science ®Google Scholar
• 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):249–255.
   PubMed Web of Science ®Google Scholar
• Dezentje 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. 2010;28(14):2423–2429.
   PubMed Web of Science ®Google Scholar
• Haque R, Shi J, Schottinger JE, et al. Tamoxifen and antidepressant drug interaction in a Cohort of 16,887 breast cancer survivors. J Natl Cancer Inst. 2016;108(3).
   Google Scholar
• Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol. 2019;37(5):423–438.
   Google Scholar
• Pagani O, Gelber S, Colleoni M, et al. Impact of SERM adherence on treatment effect: international breast cancer study group trials 13-93 and 14-93. Breast Cancer Res Treat. 2013;142(2):455–459.
   PubMed Web of Science ®Google Scholar
• Wigertz A, Ahlgren J, Holmqvist M, et al. Adherence and discontinuation of adjuvant hormonal therapy in breast cancer patients: a population-based study. Breast Cancer Res Treat. 2012;133(1):367–373.
   PubMed Web of Science ®Google Scholar
• Lash TL, Fox MP, Westrup JL, et al. Adherence to tamoxifen over the five-year course. Breast Cancer Res Treat. 2006;99(2):215–220.
   PubMed Web of Science ®Google Scholar
• Chlebowski RT, Kim J, Haque R. Adherence to endocrine therapy in breast cancer adjuvant and prevention settings. Cancer Prev Res (Phila). 2014;7(4):378–387.
   PubMed Web of Science ®Google Scholar
• Pistilli B, Paci A, Michiels S, et al. 185O_PR. Serum assessment of non-adherence to adjuvant endocrine therapy (ET) among premenopausal patients in the prospective multicenter CANTO cohort. Ann Oncol. 2018 Oct 1;29(suppl_8). Available from: https://doi.org/10.1093/annonc/mdy424.004.
   Google Scholar
• Chirgwin JH, Giobbie-Hurder A, Coates AS, et al. Treatment adherence and its impact on disease-free survival in the breast international group 1-98 trial of tamoxifen and letrozole, alone and in sequence. J Clin Oncol. 2016;34(21):2452–2459.
   PubMed Web of Science ®Google Scholar
• Lien EA, Solheim E, Kvinnsland S, et al. Identification of 4-hydroxy-N-desmethyltamoxifen as a metabolite of tamoxifen in human bile. Cancer Res. 1988;48(8):2304–2308.
   PubMed Web of Science ®Google Scholar
• Ahmad A, Ali SM, Ahmad MU, et al. Orally administered endoxifen is a new therapeutic agent for breast cancer. Breast Cancer Res Treat. 2010;122(2):579–584.
   PubMed Web of Science ®Google Scholar
• Jordan VC, Allen KE. Evaluation of the antitumour activity of the non-steroidal antioestrogen monohydroxytamoxifen in the DMBA-induced rat mammary carcinoma model. Eur J Cancer. 1980;16(2):239–251.
   PubMed Web of Science ®Google Scholar
• Hawse JR, Subramaniam M, Cicek M, et al. Endoxifen‘s molecular mechanisms of action are concentration dependent and different than that of other anti-estrogens. PLoS One. 2013;8(1):e54613.
   PubMed Web of Science ®Google Scholar
• Wu X, Hawse JR, 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):1722–1727.
   PubMed Web of Science ®Google Scholar
• Opdam FL, Dezentje VO, Den HJ, et al. The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels. Cancer Chemother Pharmacol. 2013;71(3):593–601.
   PubMed Web of Science ®Google Scholar
• Helland T, Henne N, Bifulco E, et al. Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients. Breast Cancer Res. 2017;19(1):125.
   PubMedGoogle Scholar
• Sanchez-Spitman AB, Dezentjé VO, Swen JJ, et al. A prospective study on the effect of endoxifen concentration and CYP2D6 phenotypes on clinical outcome in early stage breast cancer patients receiving adjuvant tamoxifen. J clin oncol. 2018;36(15_suppl):523.
   PubMed Web of Science ®Google Scholar
• Neven P, Jongen L, Lintermans A, et al. Tamoxifen metabolism and efficacy in breast cancer: a prospective multicenter trial. Clin Cancer Res. 2018;24(10):2312–2318.
   PubMed Web of Science ®Google Scholar
• Love RR, Desta Z, Flockhart D, et al. CYP2D6 genotypes, endoxifen levels, and disease recurrence in 224 Filipino and Vietnamese women receiving adjuvant tamoxifen for operable breast cancer. Springerplus. 2013;2(1):52.
   PubMedGoogle Scholar
• Groenland SL, Sanchez-Spitman AB, Moes DJAR, et al. 258PIncidence of clinically significant toxicities in patients with high endoxifen concentrations. Ann Oncol. 2018;29(suppl_8):mdy270.252-mdy270.252.
   Google Scholar
• Lash TL, Lien EA, Sorensen HT, et al. Genotype-guided tamoxifen therapy: time to pause for reflection? Lancet Oncol. 2009;10(8):825–833.
   PubMed Web of Science ®Google Scholar
• de Martinez DE, Ochoa AE, Blancas Lopez-Barajas I, et al. Adjusting the dose of tamoxifen in patients with early breast cancer and CYP2D6 poor metabolizer phenotype. Breast. 2014;23(4):400–406.
   PubMed Web of Science ®Google Scholar
• Dezentje VO, Opdam FL, Gelderblom H, et al. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects. Breast Cancer Res Treat. 2015;153(3):583–590.
   PubMed Web of Science ®Google Scholar