Journal Article
. 2005 Dec;23(36).
doi: 10.1200/JCO.2005.03.3266.

Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes

Matthew P Goetz 1 James M Rae  Vera J Suman  Stephanie L Safgren  Matthew M Ames  Daniel W Visscher  Carol Reynolds  Fergus J Couch  Wilma L Lingle  David A Flockhart  Zeruesenay Desta  Edith A Perez  James N Ingle  
Affiliations
  • PMID: 16361630
  •     213 citations

Abstract

Purpose: Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of tamoxifen metabolites, but their effect on clinical outcome is unknown.

Methods: We determined cytochrome P450 (CYP)2D6 (*4 and *6) and CYP3A5 (*3) genotype from paraffin-embedded tumor samples and buccal cells (living patients) in tamoxifen-treated women enrolled onto a North Central Cancer Treatment Group adjuvant breast cancer trial. The relationship between genotype and disease outcome was determined using the log-rank test and Cox proportional hazards modeling.

Results: Paraffin blocks were obtained from 223 of 256 eligible patients, and buccal cells were obtained from 17 living women. CYP2D6 (*4 and *6) and CYP3A5 (*3) genotypes were determined from 190, 194, and 205 patient samples and in 17 living women. The concordance rate between buccal and tumor genotype was 100%. Women with the CYP2D6 *4/*4 genotype had worse relapse-free time (RF-time; P = .023) and disease-free survival (DFS; P = .012), but not overall survival (P = .169) and did not experience moderate to severe hot flashes relative to women heterozygous or homozygous for the wild-type allele. In the multivariate analysis, women with the CYP2D6 *4/*4 genotype still tended to have worse RFS (hazard ratio [HR], 1.85; P = .176) and DFS (HR, 1.86; P = .089). The CYP3A5*3 variant was not associated with any of these clinical outcomes.

Conclusion: In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen.

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Clinical and biomarker predictors of side effects from tamoxifen.
Wendy Lorizio, Alan H B Wu, +4 authors, Elad Ziv.
Breast Cancer Res Treat, 2011 Dec 31; 132(3). PMID: 22207277    Free PMC article.
CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients.
James M Rae, Suzy Drury, +8 authors, ATAC trialists.
J Natl Cancer Inst, 2012 Mar 08; 104(6). PMID: 22395643    Free PMC article.
Highly Cited.
CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial.
Meredith M Regan, Brian Leyland-Jones, +18 authors, Breast International Group (BIG) 1-98 Collaborative Group.
J Natl Cancer Inst, 2012 Mar 08; 104(6). PMID: 22395644    Free PMC article.
Highly Cited.
Hormonal therapy in breast cancer: a model disease for the personalization of cancer care.
Shannon Puhalla, Saveri Bhattacharya, Nancy E Davidson.
Mol Oncol, 2012 Mar 13; 6(2). PMID: 22406404    Free PMC article.
Review.
Pharmacogenetic assessment of clinical outcome in patients with metastatic breast cancer treated with docetaxel plus capecitabine.
Ningning Dong, Jing Yu, +11 authors, Jun Ren.
J Cancer Res Clin Oncol, 2012 Mar 20; 138(7). PMID: 22426923
Building the evidence base for decision making in cancer genomic medicine using comparative effectiveness research.
Katrina A B Goddard, William A Knaus, +8 authors, David L Veenstra.
Genet Med, 2012 Apr 21; 14(7). PMID: 22516979    Free PMC article.
Review.
Tamoxifen and CYP2D6: a contradiction of data.
Daniel L Hertz, Howard L McLeod, William J Irvin.
Oncologist, 2012 Apr 26; 17(5). PMID: 22531359    Free PMC article.
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The Discriminatory Value of CYP2D6 Genotyping in Predicting the Dextromethorphan/Dextrorphan Phenotype in Women with Breast Cancer.
Andreas Trojan, Athanasios Vergopoulos, +3 authors, Wolfgang Joechle.
Breast Care (Basel), 2012 May 04; 7(1). PMID: 22553469    Free PMC article.
Personalized medicine: is it a pharmacogenetic mirage?
Rashmi R Shah, Devron R Shah.
Br J Clin Pharmacol, 2012 May 18; 74(4). PMID: 22591598    Free PMC article.
Review.
Physiologically Based Pharmacokinetic Modeling of Tamoxifen and its Metabolites in Women of Different CYP2D6 Phenotypes Provides New Insight into the Tamoxifen Mass Balance.
Kristin Dickschen, Stefan Willmann, +3 authors, Thomas Eissing.
Front Pharmacol, 2012 Jun 05; 3. PMID: 22661948    Free PMC article.
Impact of CYP2D6 polymorphism on tamoxifen therapy: where are we?
Ariana E Huber-Wechselberger, Paul Niedetzky, Irene Aigner, Elisabeth Haschke-Becher.
Wien Med Wochenschr, 2012 Jun 13; 162(11-12). PMID: 22688624
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Metabolic activity in the insular cortex and hypothalamus predicts hot flashes: an FDG-PET study.
Hadine Joffe, Thilo Deckersbach, +5 authors, Janet E Hall.
J Clin Endocrinol Metab, 2012 Jun 23; 97(9). PMID: 22723326    Free PMC article.
Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial.
I Sestak, R Kealy, +4 authors, J Cuzick.
Br J Cancer, 2012 Jun 28; 107(2). PMID: 22735900    Free PMC article.
Some applications of pharmacogenomics and epigenetics in drug development and use in pursuit of personalized medicine.
M C Powanda, E D Moyer.
Inflammopharmacology, 2012 Jul 10; 20(5). PMID: 22773313
The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice.
Philipp Y Maximov, Theresa M Lee, V Craig Jordan.
Curr Clin Pharmacol, 2012 Oct 16; 8(2). PMID: 23062036    Free PMC article.
Highly Cited. Review.
Comparative effectiveness research, genomics-enabled personalized medicine, and rapid learning health care: a common bond.
Geoffrey S Ginsburg, Nicole M Kuderer.
J Clin Oncol, 2012 Oct 17; 30(34). PMID: 23071236    Free PMC article.
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Tamoxifen use in postmenopausal breast cancer: CYP2D6 matters.
Hiltrud Brauch, Werner Schroth, +5 authors, Michel Eichelbaum.
J Clin Oncol, 2012 Oct 24; 31(2). PMID: 23091108    Free PMC article.
Trends in co-prescribing of antidepressants and tamoxifen among women with breast cancer, 2004-2010.
Stacie B Dusetzina, G Caleb Alexander, +2 authors, Nancy L Keating.
Breast Cancer Res Treat, 2012 Nov 15; 137(1). PMID: 23149465    Free PMC article.
CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8.
Matthew P Goetz, Vera J Suman, +14 authors, James N Ingle.
Clin Cancer Res, 2012 Dec 06; 19(2). PMID: 23213055    Free PMC article.
Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management.
Sarah Rofaiel, Esther N Muo, Shaker A Mousa.
Pharmgenomics Pers Med, 2010 Jan 01; 3. PMID: 23226048    Free PMC article.
CYP2D6 polymorphisms influence the efficacy of adjuvant tamoxifen in Thai breast cancer patients.
Ekaphop Sirachainan, Sureerat Jaruhathai, +6 authors, Chonlaphat Sukasem.
Pharmgenomics Pers Med, 2012 Dec 12; 5. PMID: 23226070    Free PMC article.
Functional polymorphisms in xenobiotic metabolizing enzymes and their impact on the therapy of breast cancer.
Rosane Vianna-Jorge, Juliana Simões Festa-Vasconcellos, Sheyla Maria Torres Goulart-Citrangulo, Marcelo Sobral Leite.
Front Genet, 2013 Jan 25; 3. PMID: 23346096    Free PMC article.
Pharmacogenomics of breast cancer therapy: an update.
Kelly Westbrook, Vered Stearns.
Pharmacol Ther, 2013 Mar 19; 139(1). PMID: 23500718    Free PMC article.
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Genome-wide discovery of genetic variants affecting tamoxifen sensitivity and their clinical and functional validation.
L Weng, D Ziliak, +8 authors, Consortium on Breast Cancer Pharmacogenomics (COBRA).
Ann Oncol, 2013 Mar 20; 24(7). PMID: 23508821    Free PMC article.
Variants in tamoxifen metabolizing genes: a case-control study of contralateral breast cancer risk in the WECARE study.
Jennifer D Brooks, Sharon N Teraoka, +12 authors, Jane C Figueiredo.
Int J Mol Epidemiol Genet, 2013 Apr 09; 4(1). PMID: 23565321    Free PMC article.
Tamoxifen and ovarian function.
Martine Berliere, Francois P Duhoux, +6 authors, Jean-Pascal Machiels.
PLoS One, 2013 Jul 11; 8(6). PMID: 23840510    Free PMC article.
Concordance between CYP2D6 genotypes obtained from tumor-derived and germline DNA.
James M Rae, Meredith M Regan, +8 authors, Catherine Van Poznak.
J Natl Cancer Inst, 2013 Aug 21; 105(17). PMID: 23958736    Free PMC article.
PharmGKB summary: tamoxifen pathway, pharmacokinetics.
Daniel J Klein, Caroline F Thorn, +3 authors, Teri E Klein.
Pharmacogenet Genomics, 2013 Aug 22; 23(11). PMID: 23962908    Free PMC article.
Review.
Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of Thai breast cancer patients treated with tamoxifen.
Insee Sensorn, Ekaphop Sirachainan, +5 authors, Darawan Pinthong.
Pharmgenomics Pers Med, 2013 Sep 11; 6. PMID: 24019753    Free PMC article.
Prediction of tamoxifen outcome by genetic variation of CYP2D6 in post-menopausal women with early breast cancer.
Hiltrud Brauch, Matthias Schwab.
Br J Clin Pharmacol, 2013 Sep 17; 77(4). PMID: 24033728    Free PMC article.
Frequencies of Functional Polymorphisms in Three Pharmacokinetic Genes of Clinical Interest within the Admixed Puerto Rican Population.
Carmelo Orengo-Mercado, Bianca Nieves, +5 authors, Jorge Duconge.
J Pharmacogenomics Pharmacoproteomics, 2013 Sep 17; 4(113). PMID: 24040574    Free PMC article.
Characterization of the isomeric configuration and impurities of (Z)-endoxifen by 2D NMR, high resolution LC⬜MS, and quantitative HPLC analysis.
Phyllis Elkins, Donna Coleman, +9 authors, Paul Liu.
J Pharm Biomed Anal, 2013 Sep 24; 88. PMID: 24055701    Free PMC article.
CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.
M A Province, M P Goetz, +52 authors, International Tamoxifen Pharmacogenomics Consortium.
Clin Pharmacol Ther, 2013 Sep 26; 95(2). PMID: 24060820    Free PMC article.
CYP2D6 genotype and tamoxifen response for breast cancer: a systematic review and meta-analysis.
Danny W K Lum, Pablo Perel, Aroon D Hingorani, Michael V Holmes.
PLoS One, 2013 Oct 08; 8(10). PMID: 24098545    Free PMC article.
Systematic Review.
Tamoxifen resistance in breast cancer.
Minsun Chang.
Biomol Ther (Seoul), 2012 May 01; 20(3). PMID: 24130921    Free PMC article.
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CYP19 genetic polymorphism haplotype AASA is associated with a poor prognosis in premenopausal women with lymph node-negative, hormone receptor-positive breast cancer.
Sung-Hsin Kuo, Shi-Yi Yang, +6 authors, Chiun-Sheng Huang.
Biomed Res Int, 2013 Dec 11; 2013. PMID: 24324964    Free PMC article.
In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast.
Oukseub Lee, David Ivancic, +2 authors, Seema A Khan.
Breast Cancer (Dove Med Press), 2011 Jan 01; 3. PMID: 24367176    Free PMC article.
RSF1 and not cyclin D1 gene amplification may predict lack of benefit from adjuvant tamoxifen in high-risk pre-menopausal women in the MA.12 randomized clinical trial.
Dana Keilty, Marguerite Buchanan, +6 authors, Mark Basik.
PLoS One, 2013 Dec 25; 8(12). PMID: 24367492    Free PMC article.
Hot flashes are not predictive for serum concentrations of tamoxifen and its metabolites.
Nynke G L Jager, Rutger H T Koornstra, +6 authors, Jos H Beijnen.
BMC Cancer, 2014 Jan 01; 13. PMID: 24373320    Free PMC article.
Extraction of tamoxifen and its metabolites from formalin-fixed, paraffin-embedded tissues: an innovative quantitation method using liquid chromatography and tandem mass spectrometry.
Ella S M Ng, S Bill Kangarloo, +2 authors, Anthony M Magliocco.
Cancer Chemother Pharmacol, 2014 Jan 15; 73(3). PMID: 24414550    Free PMC article.
CYP2D6 genotyping and tamoxifen in the treatment of post-menopausal breast cancer.
Per Damkier.
Br J Clin Pharmacol, 2014 Jan 23; 78(2). PMID: 24446761    Free PMC article.
Patients' understanding of how genotype variation affects benefits of tamoxifen therapy for breast cancer.
N T Brewer, J T Defrank, +13 authors, W J Irvin.
Public Health Genomics, 2014 Jan 25; 17(1). PMID: 24457521    Free PMC article.
Re: Concordance between CYP2D6 genotypes obtained from tumor-derived and germline DNA.
Matthew P Goetz, Hiltrud Brauch, +4 authors, James N Ingle.
J Natl Cancer Inst, 2014 Apr 05; 106(5). PMID: 24700804    Free PMC article.
The effects of a novel hormonal breast cancer therapy, endoxifen, on the mouse skeleton.
Anne Gingery, Malayannan Subramaniam, +9 authors, John R Hawse.
PLoS One, 2014 May 24; 9(5). PMID: 24853369    Free PMC article.
Drug resistance to targeted therapies: déjà vu all over again.
Floris H Groenendijk, René Bernards.
Mol Oncol, 2014 Jun 10; 8(6). PMID: 24910388    Free PMC article.
Highly Cited. Review.
A randomized phase II presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast.
Oukseub Lee, Katherine Page, +19 authors, Seema A Khan.
Clin Cancer Res, 2014 Jul 17; 20(14). PMID: 25028506    Free PMC article.
CYP2D6 genotype and tamoxifen: considerations for proper nonprospective studies.
M P Goetz, J N Ingle.
Clin Pharmacol Ther, 2014 Jul 25; 96(2). PMID: 25056392    Free PMC article.
Review.
Simulation with cells in vitro of tamoxifen treatment in premenopausal breast cancer patients with different CYP2D6 genotypes.
Philipp Y Maximov, Russell E McDaniel, +5 authors, V Craig Jordan.
Br J Pharmacol, 2014 Jul 31; 171(24). PMID: 25073551    Free PMC article.
Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen.
Christos Markopoulos, Stylianos Kykalos, Dimitrios Mantas.
World J Clin Oncol, 2014 Aug 13; 5(3). PMID: 25114852    Free PMC article.
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Preventing breast cancer in LMICs via screening and/or early detection: The real and the surreal.
Subhojit Dey.
World J Clin Oncol, 2014 Aug 13; 5(3). PMID: 25114864    Free PMC article.
Review.
Determination of CYP2D6 *3, *4, and *10 frequency in women with breast cancer in São Luís, Brazil, and its association with prognostic factors and disease-free survival.
D M F Martins, F C B Vidal, +2 authors, L M O Brito.
Braz J Med Biol Res, 2014 Oct 09; 47(11). PMID: 25296365    Free PMC article.
Loss of heterozygosity at the CYP2D6 locus in breast cancer: implications for germline pharmacogenetic studies.
Matthew P Goetz, James X Sun, +19 authors, Roman Yelensky.
J Natl Cancer Inst, 2014 Dec 11; 107(2). PMID: 25490892    Free PMC article.
Germline oncopharmacogenetics, a promising field in cancer therapy.
Chiara Pesenti, Milena Gusella, Silvia M Sirchia, Monica Miozzo.
Cell Oncol (Dordr), 2015 Jan 13; 38(1). PMID: 25573079
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The potential of translational bioinformatics approaches for pharmacology research.
Lang Li.
Br J Clin Pharmacol, 2015 Mar 11; 80(4). PMID: 25753093    Free PMC article.
Course and Moderators of Hot Flash Interference during Androgen Deprivation Therapy for Prostate Cancer: A Matched Comparison.
Brian D Gonzalez, Heather S L Jim, +7 authors, Paul B Jacobsen.
J Urol, 2015 Mar 21; 194(3). PMID: 25791402    Free PMC article.
Mechanisms of endocrine resistance in breast cancer: an overview of the proposed roles of noncoding RNA.
Erin L Hayes, Joan S Lewis-Wambi.
Breast Cancer Res, 2015 Apr 08; 17. PMID: 25849966    Free PMC article.
Highly Cited. Review.
Effects of Pharmacogenetics on the Pharmacokinetics and Pharmacodynamics of Tamoxifen.
Aurelia H M de Vries Schultink, Wilbert Zwart, +2 authors, Alwin D R Huitema.
Clin Pharmacokinet, 2015 May 06; 54(8). PMID: 25940823    Free PMC article.
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Tamoxifen induces a pluripotency signature in breast cancer cells and human tumors.
George Notas, Vassiliki Pelekanou, +8 authors, Elias Castanas.
Mol Oncol, 2015 Jun 28; 9(9). PMID: 26115764    Free PMC article.
Limited predictive value of achieving beneficial plasma (Z)-endoxifen threshold level by CYP2D6 genotyping in tamoxifen-treated Polish women with breast cancer.
Ewa E Hennig, Magdalena Piatkowska, +8 authors, Jerzy Ostrowski.
BMC Cancer, 2015 Aug 02; 15. PMID: 26232141    Free PMC article.
Genotyping concordance in DNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor and whole blood for pharmacogenetic analyses.
Daniel L Hertz, Kelley M Kidwell, +7 authors, James M Rae.
Mol Oncol, 2015 Aug 16; 9(9). PMID: 26276228    Free PMC article.
CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects.
V O Dezentjé, F L Opdam, +11 authors, H-J Guchelaar.
Breast Cancer Res Treat, 2015 Sep 16; 153(3). PMID: 26369533    Free PMC article.
Tamoxifen and Antidepressant Drug Interaction in a Cohort of 16,887 Breast Cancer Survivors.
Reina Haque, Jiaxiao Shi, +8 authors, Marilyn L Kwan.
J Natl Cancer Inst, 2015 Dec 04; 108(3). PMID: 26631176    Free PMC article.
ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen.
Insee Sensorn, Chonlaphat Sukasem, +6 authors, Sansanee Wongwaisayawan.
Onco Targets Ther, 2016 Apr 26; 9. PMID: 27110128    Free PMC article.
Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity.
Daniel L Hertz, Allison Deal, +19 authors, William J Irvin.
Oncologist, 2016 May 27; 21(7). PMID: 27226358    Free PMC article.
Linker design for the modular assembly of multifunctional and targeted platinum(ii)-containing anticancer agents.
S Ding, U Bierbach.
Dalton Trans, 2016 Jun 03; 45(33). PMID: 27251881    Free PMC article.
The Impact of CYP2D6 Genotyping on Tamoxifen Treatment.
Roberta Ferraldeschi, William G Newman.
Pharmaceuticals (Basel), 2010 Apr 15; 3(4). PMID: 27713292    Free PMC article.
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Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine.
Shabbir Ahmed, Zhan Zhou, Jie Zhou, Shu-Qing Chen.
Genomics Proteomics Bioinformatics, 2016 Oct 31; 14(5). PMID: 27729266    Free PMC article.
Review.
Cytochrome P-450 2D6 (CYP2D6) Genotype and Breast Cancer Recurrence in Tamoxifen-Treated Patients: Evaluating the Importance of Loss of Heterozygosity.
Thomas P Ahern, Daniel L Hertz, +7 authors, Deirdre P Cronin-Fenton.
Am J Epidemiol, 2016 Dec 19; 185(2). PMID: 27988492    Free PMC article.
Review.
Molecular mechanisms and mode of tamoxifen resistance in breast cancer.
Shazia Ali, Mahmood Rasool, +9 authors, Mohammad Sarwar Jamal.
Bioinformation, 2017 Feb 06; 12(3). PMID: 28149048    Free PMC article.
Review.
Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women's Health Initiative Study.
Carolyn J Crandall, JoAnn E Manson, +6 authors, Janet S Sinsheimer.
Menopause, 2017 Feb 24; 24(3). PMID: 28231077    Free PMC article.
An inter-professional approach to personalized medicine education: one institution's experience.
Christine M Formea, Wayne T Nicholson, Carolyn Rohrer Vitek.
Per Med, 2015 Mar 01; 12(2). PMID: 28413426    Free PMC article.
Tumoral expression of drug and xenobiotic metabolizing enzymes in breast cancer patients of different ethnicities with implications to personalized medicine.
Yan Li, Albert Steppi, +6 authors, Jinfeng Zhang.
Sci Rep, 2017 Jul 08; 7(1). PMID: 28684774    Free PMC article.
CYP2D6 genotype is not associated with survival in breast cancer patients treated with tamoxifen: results from a population-based study.
D L Hertz, K M Kidwell, +8 authors, J M Rae.
Breast Cancer Res Treat, 2017 Jul 22; 166(1). PMID: 28730340    Free PMC article.
First-in-Human Phase I Study of the Tamoxifen Metabolite Z-Endoxifen in Women With Endocrine-Refractory Metastatic Breast Cancer.
Matthew P Goetz, Vera J Suman, +23 authors, James N Ingle.
J Clin Oncol, 2017 Aug 31; 35(30). PMID: 28854070    Free PMC article.
Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients.
Thomas Helland, Nina Henne, +12 authors, Håvard Søiland.
Breast Cancer Res, 2017 Dec 01; 19(1). PMID: 29183390    Free PMC article.
Translational Biomedical Informatics and Pharmacometrics Approaches in the Drug Interactions Research.
Pengyue Zhang, Heng-Yi Wu, +6 authors, Lang Li.
CPT Pharmacometrics Syst Pharmacol, 2017 Dec 02; 7(2). PMID: 29193890    Free PMC article.
Review.
Pharmacogenomics Guided-Personalization of Warfarin and Tamoxifen.
Theodore J Wigle, Laura E Jansen, Wendy A Teft, Richard B Kim.
J Pers Med, 2017 Dec 14; 7(4). PMID: 29236081    Free PMC article.
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Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy.
Matthew P Goetz, Katrin Sangkuhl, +12 authors, Teri E Klein.
Clin Pharmacol Ther, 2018 Feb 01; 103(5). PMID: 29385237    Free PMC article.
Highly Cited.
Endocrine Treatment-Related Symptoms and Patient Outcomes in Breast Cancer: A Meta-Analysis.
Tae-Kyung Yoo, Myoung-Jin Jang, +3 authors, Wonshik Han.
J Breast Cancer, 2018 Apr 10; 21(1). PMID: 29628982    Free PMC article.
Endocrine therapy for breast cancer in the primary care setting.
A Awan, K Esfahani.
Curr Oncol, 2018 Aug 17; 25(4). PMID: 30111969    Free PMC article.
A genome-wide association study identifies three novel genetic markers for response to tamoxifen: A prospective multicenter study.
Hiroshi Onishi, Chihiro Udagawa, +31 authors, Hitoshi Zembutsu.
PLoS One, 2018 Aug 31; 13(8). PMID: 30161160    Free PMC article.
Structure establishment of three-dimensional (3D) cell culture printing model for bladder cancer.
Myeong Joo Kim, Byung Hoon Chi, +3 authors, In Ho Chang.
PLoS One, 2019 Oct 23; 14(10). PMID: 31639124    Free PMC article.
Hormonal status affects plasma exposure of tamoxifen and its main metabolites in tamoxifen-treated breast cancer patients.
João Paulo Bianchi Ximenez, Jurandyr Moreira de Andrade, +3 authors, Vera Lucia Lanchote.
BMC Pharmacol Toxicol, 2019 Dec 20; 20(Suppl 1). PMID: 31852530    Free PMC article.
CYP2D6 Genotype Predicts Tamoxifen Discontinuation and Prognosis in Patients With Breast Cancer.
Wei He, Felix Grassmann, +5 authors, Kamila Czene.
J Clin Oncol, 2019 Dec 05; 38(6). PMID: 31800347    Free PMC article.
Lobular breast carcinoma metastatic to the endometrium in a patient under tamoxifen therapy: A case report.
Mariangela Gomez, Kerry Whitting, Rana Naous.
SAGE Open Med Case Rep, 2020 Feb 29; 8. PMID: 32110411    Free PMC article.
Estrogens and breast cancer: Mechanisms involved in obesity-related development, growth and progression.
Priya Bhardwaj, CheukMan C Au, +4 authors, Kristy A Brown.
J Steroid Biochem Mol Biol, 2019 Mar 10; 189. PMID: 30851382    Free PMC article.
Review.
Targeted ultra-deep sequencing of a South African Bantu-speaking cohort to comprehensively map and characterize common and novel variants in 65 pharmacologically-related genes.
Sibongile Tshabalala, Ananyo Choudhury, +3 authors, Dalu Mancama.
Pharmacogenet Genomics, 2019 Jun 05; 29(7). PMID: 31162291    Free PMC article.
Metabolic Pathway Analysis and Effectiveness of Tamoxifen in Danish Breast Cancer Patients.
Thomas P Ahern, Lindsay J Collin, +16 authors, Deirdre Cronin-Fenton.
Cancer Epidemiol Biomarkers Prev, 2020 Jan 15; 29(3). PMID: 31932415    Free PMC article.
Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, in vitro and in human tumor xenograft models.
Fei Long, Ye He, +6 authors, Liguang Lou.
Cancer Sci, 2019 Feb 07; 110(4). PMID: 30724426    Free PMC article.
Integrated Data Analysis of Six Clinical Studies Points Toward Model-Informed Precision Dosing of Tamoxifen.
Lena Klopp-Schulze, Anna Mueller-Schoell, +4 authors, Charlotte Kloft.
Front Pharmacol, 2020 Apr 17; 11. PMID: 32296331    Free PMC article.
Tamoxifen Metabolism and Breast Cancer Recurrence: A Question Unanswered by CYPTAM.
Matthew P Goetz, Vera J Suman, +3 authors, James N Ingle.
J Clin Oncol, 2019 Jun 19; 37(22). PMID: 31211604    Free PMC article.
Enhanced Activity of P4503A4 and UGT1A10 Induced by Acridinone Derivatives C-1305 and C-1311 in MCF-7 and HCT116 Cancer Cells: Consequences for the Drugs' Cytotoxicity, Metabolism and Cellular Response.
Monika Pawłowska, Anna Kwaśniewska, Zofia Mazerska, Ewa Augustin.
Int J Mol Sci, 2020 Jun 04; 21(11). PMID: 32486425    Free PMC article.
The Roles of Common Variation and Somatic Mutation in Cancer Pharmacogenomics.
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Oncol Ther, 2020 Jul 24; 7(1). PMID: 32700193    Free PMC article.
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A Polymorphism within the Vitamin D Transporter Gene Predicts Outcome in Metastatic Colorectal Cancer Patients Treated with FOLFIRI/Bevacizumab or FOLFIRI/Cetuximab.
Martin D Berger, Sebastian Stintzing, +17 authors, Heinz-Josef Lenz.
Clin Cancer Res, 2017 Dec 07; 24(4). PMID: 29208668    Free PMC article.
Inhibition of tumor growth and angiogenesis of tamoxifen-resistant breast cancer cells by ruxolitinib, a selective JAK2 inhibitor.
Ji Won Kim, Jaya Gautam, +2 authors, Keon Wook Kang.
Oncol Lett, 2019 Apr 02; 17(4). PMID: 30930994    Free PMC article.
Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites.
Zahra Khalaj, Zohreh Baratieh, +7 authors, Mansoor Salehi.
Front Pharmacol, 2019 Jun 11; 10. PMID: 31178724    Free PMC article.
LINC00309 is associated with short disease-free survival in breast cancer.
Sheng Huang, Yayun Chi, +10 authors, Jiong Wu.
Cancer Cell Int, 2019 Aug 14; 19. PMID: 31406486    Free PMC article.
Genetic Variation and Hot Flashes: A Systematic Review.
Carolyn J Crandall, Allison L Diamant, +2 authors, Janet Sinsheimer.
J Clin Endocrinol Metab, 2020 Aug 17; 105(12). PMID: 32797194    Free PMC article.
Systematic Review.
Polymorphic variants of drug-metabolizing enzymes alter the risk and survival of oral cancer patients.
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3 Biotech, 2020 Nov 21; 10(12). PMID: 33214976    Free PMC article.
Outcomes of Japanese breast cancer patients treated with pre-operative and post-operative anastrozole or tamoxifen.
Yasuhiro Fujiwara, Yuichi Takatsuka, +8 authors, Shinzaburo Noguchi.
Cancer Sci, 2011 Dec 06; 103(3). PMID: 22136317    Free PMC article.
Pharmacogenomics, CYP2D6, and Tamoxifen: A Survey of the Reasons Sustaining European Clinical Practice Paradigms.
Sara S Reis, Ana S Carvalho, Rúben Fernandes.
Medicina (Kaunas), 2019 Jul 10; 55(7). PMID: 31284530    Free PMC article.
Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse.
A B Sanchez-Spitman, J J Swen, +3 authors, H J Guchelaar.
Sci Rep, 2021 Jan 13; 11(1). PMID: 33432065    Free PMC article.
Bayesian Pathway Analysis for Complex Interactions.
James W Baurley, Anders Kjærsgaard, +6 authors, Thomas P Ahern.
Am J Epidemiol, 2020 Jul 09; 189(12). PMID: 32639515    Free PMC article.
Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy.
Tessa A M Mulder, Mirjam de With, +3 authors, Ron H N van Schaik.
Cancers (Basel), 2021 Mar 07; 13(4). PMID: 33673305    Free PMC article.
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The Role of CYP2D6 Polymorphisms in Determining Response to Tamoxifen in Metastatic Breast Cancer Patients: Review and Egyptian Experience.
Ibrahim Malash, Osman Mansour, +6 authors, Abeer Bahnassy.
Asian Pac J Cancer Prev, 2020 Dec 29; 21(12). PMID: 33369460    Free PMC article.