CYP3A4 and seasonal variation in vitamin D status in addition to CYP2D6 contribute to therapeutic endoxifen level during tamoxifen therapy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-05

AUTHORS

Wendy A. Teft, Inna Y. Gong, Brian Dingle, Kylea Potvin, Jawaid Younus, Theodore A. Vandenberg, Muriel Brackstone, Francisco E. Perera, Yun-Hee Choi, Guangyong Zou, Robin M. Legan, Rommel G. Tirona, Richard B. Kim

ABSTRACT

Tamoxifen is a widely utilized adjuvant anti-estrogen agent for hormone receptor-positive breast cancer, known to undergo CYP2D6-mediated bioactivation to endoxifen. However, little is known regarding additional genetic and non-genetic determinants of optimal endoxifen plasma concentration. Therefore, 196 breast cancer patients on tamoxifen were enrolled in this prospective study over a 24-month period. Blood samples were collected for pharmacogenetic and drug-level analysis of tamoxifen and metabolites. Regression analysis indicated that besides CYP2D6, the recently described CYP3A4*22 genotype, seasonal variation, and concomitant use of CYP2D6-inhibiting antidepressants were significant predictors of endoxifen concentration. Of note, genetic variation explained 33 % of the variability while non-genetic variables accounted for 13 %. Given the proposed notion of a sub-therapeutic endoxifen concentration for predicting breast cancer recurrence, we set the therapeutic threshold at 18 nM, the 20th percentile for endoxifen level among enrolled patients in this cohort. Nearly 70 % of CYP2D6 poor metabolizers as well as extensive metabolizers on potent CYP2D6-inhibiting antidepressants exhibited endoxifen levels below 18 nM, while carriers of CYP3A4*22 were twofold less likely to be in sub-therapeutic range. Unexpectedly, endoxifen levels were 20 % lower during winter months than mean levels across seasons, which was also associated with lower vitamin D levels. CYP3A4*22 genotype along with sunshine exposure and vitamin D status may be unappreciated contributors of tamoxifen efficacy. The identified covariates along with demographic variables were integrated to create an endoxifen concentration prediction algorithm to pre-emptively evaluate the likelihood of individual patients falling below the optimal endoxifen concentration. More... »

PAGES

95-105

References to SciGraph publications

  • 2012-07. Effects of CYP Induction by Rifampicin on Tamoxifen Exposure in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2011-08. Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs in THE PHARMACOGENOMICS JOURNAL
  • 2007-02. Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer in BREAST CANCER RESEARCH
  • 2006-07. Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: Implication for optimization of breast cancer treatment in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2011-08. Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study in BREAST CANCER RESEARCH
  • 2005-05. Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifen in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 2013-05. Determination of clinically therapeutic endoxifen concentrations based on efficacy from human MCF7 breast cancer xenografts in BREAST CANCER RESEARCH AND TREATMENT
  • 2011-08. Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in Finland in EUROPEAN JOURNAL OF NUTRITION
  • 2011-05. Tamoxifen Metabolite Concentrations, CYP2D6 Genotype, and Breast Cancer Outcomes in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2007-01. The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen in BREAST CANCER RESEARCH AND TREATMENT
  • 2011-05. 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 in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2009-08. CYP2D6 and tamoxifen: DNA matters in breast cancer in NATURE REVIEWS CANCER
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s10549-013-2511-4

    DOI

    http://dx.doi.org/10.1007/s10549-013-2511-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1028649218

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23580071


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Adult", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Aged", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Aged, 80 and over", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antineoplastic Agents", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Breast Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cytochrome P-450 CYP2D6", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cytochrome P-450 CYP3A", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genotype", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Middle Aged", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Seasons", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tamoxifen", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Vitamin D", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Teft", 
            "givenName": "Wendy A.", 
            "id": "sg:person.01035436656.70", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01035436656.70"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, ON, Canada", 
                "Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gong", 
            "givenName": "Inna Y.", 
            "id": "sg:person.0766401110.25", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0766401110.25"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Department of Oncology, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Dingle", 
            "givenName": "Brian", 
            "id": "sg:person.0605663452.12", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605663452.12"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Department of Oncology, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Potvin", 
            "givenName": "Kylea", 
            "id": "sg:person.0711137447.78", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0711137447.78"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Department of Oncology, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Younus", 
            "givenName": "Jawaid", 
            "id": "sg:person.0770225252.63", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0770225252.63"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Department of Oncology, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Vandenberg", 
            "givenName": "Theodore A.", 
            "id": "sg:person.01057073130.12", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01057073130.12"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Department of Oncology, University of Western Ontario, London, ON, Canada", 
                "Department of Surgery, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Brackstone", 
            "givenName": "Muriel", 
            "id": "sg:person.01061024446.05", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01061024446.05"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Department of Oncology, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Perera", 
            "givenName": "Francisco E.", 
            "id": "sg:person.01027032555.87", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01027032555.87"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Choi", 
            "givenName": "Yun-Hee", 
            "id": "sg:person.01261612231.85", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01261612231.85"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zou", 
            "givenName": "Guangyong", 
            "id": "sg:person.0730570317.59", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0730570317.59"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Legan", 
            "givenName": "Robin M.", 
            "id": "sg:person.0765260642.03", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0765260642.03"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Western University", 
              "id": "https://www.grid.ac/institutes/grid.39381.30", 
              "name": [
                "Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, ON, Canada", 
                "Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tirona", 
            "givenName": "Rommel G.", 
            "id": "sg:person.01240340342.20", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01240340342.20"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "London Health Sciences Centre", 
              "id": "https://www.grid.ac/institutes/grid.412745.1", 
              "name": [
                "Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, ON, Canada", 
                "Department of Oncology, University of Western Ontario, London, ON, Canada", 
                "Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada", 
                "Department of Medicine, LHSC-University Hospital, Room A-LL-152, 339 Windermere Road, N6A 5A5, London, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kim", 
            "givenName": "Richard B.", 
            "id": "sg:person.015716462057.79", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015716462057.79"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1124/jpet.108.149815", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000514154"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0169-409x(02)00066-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000686994"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0169-409x(02)00066-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000686994"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00280-004-0926-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003611498", 
              "https://doi.org/10.1007/s00280-004-0926-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00280-004-0926-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003611498", 
              "https://doi.org/10.1007/s00280-004-0926-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0710615105", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003974980"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/clpt.2011.32", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005561058", 
              "https://doi.org/10.1038/clpt.2011.32"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10549-006-9428-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007965097", 
              "https://doi.org/10.1007/s10549-006-9428-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10549-006-9428-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007965097", 
              "https://doi.org/10.1007/s10549-006-9428-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/clpt.2011.372", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011168548", 
              "https://doi.org/10.1038/clpt.2011.372"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1146/annurev-med-070909-182545", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013300668"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-08-3933", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014845611"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1016/j.clpt.2006.03.013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018855231", 
              "https://doi.org/10.1016/j.clpt.2006.03.013"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/bcr2920", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019004438", 
              "https://doi.org/10.1186/bcr2920"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1124/jpet.104.065607", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019953192"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/clpt.2011.27", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022654582", 
              "https://doi.org/10.1038/clpt.2011.27"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/clpt.2011.27", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022654582", 
              "https://doi.org/10.1038/clpt.2011.27"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1056/nejmra032424", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024080521"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jnci/djs126", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027165104"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/tpj.2010.28", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027819854", 
              "https://doi.org/10.1038/tpj.2010.28"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00394-010-0138-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029315523", 
              "https://doi.org/10.1007/s00394-010-0138-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc2683", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032860958", 
              "https://doi.org/10.1038/nrc2683"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc2683", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032860958", 
              "https://doi.org/10.1038/nrc2683"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/bcr1640", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033336327", 
              "https://doi.org/10.1186/bcr1640"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/bcr1640", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033336327", 
              "https://doi.org/10.1186/bcr1640"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0140-6736(97)11423-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033560955"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2010.32.9839", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035143430"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jnci/djs125", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035302715"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jnci/dji005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036118248"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.bcp.2012.03.017", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037122369"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1124/dmd.110.036160", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039200983"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2010.31.4427", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041583874"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1365-2125.2010.03773.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043371222"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1001/jama.2009.1420", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044667494"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1634/theoncologist.2011-0418", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044929077"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10549-013-2530-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045716766", 
              "https://doi.org/10.1007/s10549-013-2530-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/aje/kwr091", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046237680"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2009.25.7246", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050357972"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1078-0432.ccr-12-2153", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052002227"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/fpc.0b013e32833225e7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1060340765"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/fpc.0b013e32833225e7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1060340765"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/fpc.0b013e32833225e7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1060340765"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/fpc.0b013e32833225e7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1060340765"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1176/appi.ajp.2008.08040482", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1063498247"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1124/mol.60.6.1399", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1074958474"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1078549673", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1124/mol.51.5.741", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1083087429"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2013-05", 
        "datePublishedReg": "2013-05-01", 
        "description": "Tamoxifen is a widely utilized adjuvant anti-estrogen agent for hormone receptor-positive breast cancer, known to undergo CYP2D6-mediated bioactivation to endoxifen. However, little is known regarding additional genetic and non-genetic determinants of optimal endoxifen plasma concentration. Therefore, 196 breast cancer patients on tamoxifen were enrolled in this prospective study over a 24-month period. Blood samples were collected for pharmacogenetic and drug-level analysis of tamoxifen and metabolites. Regression analysis indicated that besides CYP2D6, the recently described CYP3A4*22 genotype, seasonal variation, and concomitant use of CYP2D6-inhibiting antidepressants were significant predictors of endoxifen concentration. Of note, genetic variation explained 33 % of the variability while non-genetic variables accounted for 13 %. Given the proposed notion of a sub-therapeutic endoxifen concentration for predicting breast cancer recurrence, we set the therapeutic threshold at 18 nM, the 20th percentile for endoxifen level among enrolled patients in this cohort. Nearly 70 % of CYP2D6 poor metabolizers as well as extensive metabolizers on potent CYP2D6-inhibiting antidepressants exhibited endoxifen levels below 18 nM, while carriers of CYP3A4*22 were twofold less likely to be in sub-therapeutic range. Unexpectedly, endoxifen levels were 20 % lower during winter months than mean levels across seasons, which was also associated with lower vitamin D levels. CYP3A4*22 genotype along with sunshine exposure and vitamin D status may be unappreciated contributors of tamoxifen efficacy. The identified covariates along with demographic variables were integrated to create an endoxifen concentration prediction algorithm to pre-emptively evaluate the likelihood of individual patients falling below the optimal endoxifen concentration.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1007/s10549-013-2511-4", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1092777", 
            "issn": [
              "0167-6806", 
              "1573-7217"
            ], 
            "name": "Breast Cancer Research and Treatment", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "139"
          }
        ], 
        "name": "CYP3A4 and seasonal variation in vitamin D status in addition to CYP2D6 contribute to therapeutic endoxifen level during tamoxifen therapy", 
        "pagination": "95-105", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "8879c6a8bd9959cca0732c3a712957b979bba01572f12de68794a855f53ffeb8"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "23580071"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "8111104"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1007/s10549-013-2511-4"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1028649218"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1007/s10549-013-2511-4", 
          "https://app.dimensions.ai/details/publication/pub.1028649218"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-10T15:52", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8664_00000513.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://link.springer.com/10.1007%2Fs10549-013-2511-4"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s10549-013-2511-4'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s10549-013-2511-4'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s10549-013-2511-4'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s10549-013-2511-4'


     

    This table displays all metadata directly associated to this object as RDF triples.

    344 TRIPLES      21 PREDICATES      81 URIs      35 LITERALS      23 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1007/s10549-013-2511-4 schema:about N0c787dabb08245a19dd6701c2db6dbee
    2 N0fd0564e0cee4ee9988e30fe3638fa75
    3 N17db36a869834b79ad2227d1a281ee6b
    4 N1a33e5c291b44a4b97fc88a16edb0241
    5 N28d3f36a21b94ddfbbf2675174b6c055
    6 N421c015542cd44f286c938c72a7e6c32
    7 N4585b235ecd34736a5c3d10300ca02bc
    8 N58acd562c8e64446bd6e2955fe26fdac
    9 N733f1391e09c402c87f8f8ffd0b68c5f
    10 Nb1c430a8be5b45f79cf218656b0f0d75
    11 Nba757868ab2a4bfe90e0649cb3b97115
    12 Nc5f2ec5ab6df415da0b08c9eedfcd201
    13 Nd95d4c0ad6164df9bbe51c9248722264
    14 Ne78cfa54a2164200b6bea3fb36671496
    15 anzsrc-for:11
    16 anzsrc-for:1112
    17 schema:author N3b32129efc614ae89adcd2f0f5883ef0
    18 schema:citation sg:pub.10.1007/s00280-004-0926-7
    19 sg:pub.10.1007/s00394-010-0138-3
    20 sg:pub.10.1007/s10549-006-9428-0
    21 sg:pub.10.1007/s10549-013-2530-1
    22 sg:pub.10.1016/j.clpt.2006.03.013
    23 sg:pub.10.1038/clpt.2011.27
    24 sg:pub.10.1038/clpt.2011.32
    25 sg:pub.10.1038/clpt.2011.372
    26 sg:pub.10.1038/nrc2683
    27 sg:pub.10.1038/tpj.2010.28
    28 sg:pub.10.1186/bcr1640
    29 sg:pub.10.1186/bcr2920
    30 https://app.dimensions.ai/details/publication/pub.1078549673
    31 https://doi.org/10.1001/jama.2009.1420
    32 https://doi.org/10.1016/j.bcp.2012.03.017
    33 https://doi.org/10.1016/s0140-6736(97)11423-4
    34 https://doi.org/10.1016/s0169-409x(02)00066-2
    35 https://doi.org/10.1056/nejmra032424
    36 https://doi.org/10.1073/pnas.0710615105
    37 https://doi.org/10.1093/aje/kwr091
    38 https://doi.org/10.1093/jnci/dji005
    39 https://doi.org/10.1093/jnci/djs125
    40 https://doi.org/10.1093/jnci/djs126
    41 https://doi.org/10.1097/fpc.0b013e32833225e7
    42 https://doi.org/10.1111/j.1365-2125.2010.03773.x
    43 https://doi.org/10.1124/dmd.110.036160
    44 https://doi.org/10.1124/jpet.104.065607
    45 https://doi.org/10.1124/jpet.108.149815
    46 https://doi.org/10.1124/mol.51.5.741
    47 https://doi.org/10.1124/mol.60.6.1399
    48 https://doi.org/10.1146/annurev-med-070909-182545
    49 https://doi.org/10.1158/0008-5472.can-08-3933
    50 https://doi.org/10.1158/1078-0432.ccr-12-2153
    51 https://doi.org/10.1176/appi.ajp.2008.08040482
    52 https://doi.org/10.1200/jco.2009.25.7246
    53 https://doi.org/10.1200/jco.2010.31.4427
    54 https://doi.org/10.1200/jco.2010.32.9839
    55 https://doi.org/10.1634/theoncologist.2011-0418
    56 schema:datePublished 2013-05
    57 schema:datePublishedReg 2013-05-01
    58 schema:description Tamoxifen is a widely utilized adjuvant anti-estrogen agent for hormone receptor-positive breast cancer, known to undergo CYP2D6-mediated bioactivation to endoxifen. However, little is known regarding additional genetic and non-genetic determinants of optimal endoxifen plasma concentration. Therefore, 196 breast cancer patients on tamoxifen were enrolled in this prospective study over a 24-month period. Blood samples were collected for pharmacogenetic and drug-level analysis of tamoxifen and metabolites. Regression analysis indicated that besides CYP2D6, the recently described CYP3A4*22 genotype, seasonal variation, and concomitant use of CYP2D6-inhibiting antidepressants were significant predictors of endoxifen concentration. Of note, genetic variation explained 33 % of the variability while non-genetic variables accounted for 13 %. Given the proposed notion of a sub-therapeutic endoxifen concentration for predicting breast cancer recurrence, we set the therapeutic threshold at 18 nM, the 20th percentile for endoxifen level among enrolled patients in this cohort. Nearly 70 % of CYP2D6 poor metabolizers as well as extensive metabolizers on potent CYP2D6-inhibiting antidepressants exhibited endoxifen levels below 18 nM, while carriers of CYP3A4*22 were twofold less likely to be in sub-therapeutic range. Unexpectedly, endoxifen levels were 20 % lower during winter months than mean levels across seasons, which was also associated with lower vitamin D levels. CYP3A4*22 genotype along with sunshine exposure and vitamin D status may be unappreciated contributors of tamoxifen efficacy. The identified covariates along with demographic variables were integrated to create an endoxifen concentration prediction algorithm to pre-emptively evaluate the likelihood of individual patients falling below the optimal endoxifen concentration.
    59 schema:genre research_article
    60 schema:inLanguage en
    61 schema:isAccessibleForFree false
    62 schema:isPartOf N766f5c22f6bb48e8ab90ccc594363abb
    63 Nb7ea9905ecdb4e9dbce070f64dff887e
    64 sg:journal.1092777
    65 schema:name CYP3A4 and seasonal variation in vitamin D status in addition to CYP2D6 contribute to therapeutic endoxifen level during tamoxifen therapy
    66 schema:pagination 95-105
    67 schema:productId N2179a3a97b524663813d102afd3e99d4
    68 N31ad1bad15fe4dcaabba0137acb3ea4e
    69 N99d0f95cf8264538a89de4238f007666
    70 N9fd3df4dbe434aa9b5a2414e95e885e0
    71 Nf46b3380f9a54d8fb6c7ed0e094faaa4
    72 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028649218
    73 https://doi.org/10.1007/s10549-013-2511-4
    74 schema:sdDatePublished 2019-04-10T15:52
    75 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    76 schema:sdPublisher N7685235f935d4ba6808c5c0ced85f87c
    77 schema:url http://link.springer.com/10.1007%2Fs10549-013-2511-4
    78 sgo:license sg:explorer/license/
    79 sgo:sdDataset articles
    80 rdf:type schema:ScholarlyArticle
    81 N07401f48317d403bb82428aeb50b398d rdf:first sg:person.01027032555.87
    82 rdf:rest Need515f7b34146df981e94c022f6a04e
    83 N0c787dabb08245a19dd6701c2db6dbee schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    84 schema:name Antineoplastic Agents
    85 rdf:type schema:DefinedTerm
    86 N0fd0564e0cee4ee9988e30fe3638fa75 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    87 schema:name Humans
    88 rdf:type schema:DefinedTerm
    89 N17db36a869834b79ad2227d1a281ee6b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    90 schema:name Aged
    91 rdf:type schema:DefinedTerm
    92 N1a33e5c291b44a4b97fc88a16edb0241 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    93 schema:name Adult
    94 rdf:type schema:DefinedTerm
    95 N2179a3a97b524663813d102afd3e99d4 schema:name readcube_id
    96 schema:value 8879c6a8bd9959cca0732c3a712957b979bba01572f12de68794a855f53ffeb8
    97 rdf:type schema:PropertyValue
    98 N28d3f36a21b94ddfbbf2675174b6c055 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    99 schema:name Cytochrome P-450 CYP3A
    100 rdf:type schema:DefinedTerm
    101 N31ad1bad15fe4dcaabba0137acb3ea4e schema:name doi
    102 schema:value 10.1007/s10549-013-2511-4
    103 rdf:type schema:PropertyValue
    104 N3b32129efc614ae89adcd2f0f5883ef0 rdf:first sg:person.01035436656.70
    105 rdf:rest N3d726d9032e14389b4479bacc65b9e0e
    106 N3d726d9032e14389b4479bacc65b9e0e rdf:first sg:person.0766401110.25
    107 rdf:rest Nb68301a32a76404fa777ccf0a2fb65b7
    108 N421c015542cd44f286c938c72a7e6c32 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    109 schema:name Seasons
    110 rdf:type schema:DefinedTerm
    111 N4585b235ecd34736a5c3d10300ca02bc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    112 schema:name Genotype
    113 rdf:type schema:DefinedTerm
    114 N49f5a4e4440540eabbb9a666593e75e3 rdf:first sg:person.01061024446.05
    115 rdf:rest N07401f48317d403bb82428aeb50b398d
    116 N541215417a864daab2b372567b30ccb5 rdf:first sg:person.0770225252.63
    117 rdf:rest N89d3851334cf4efe9ba6475d82f299e6
    118 N58acd562c8e64446bd6e2955fe26fdac schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    119 schema:name Aged, 80 and over
    120 rdf:type schema:DefinedTerm
    121 N5a20b9633bea4a82abc9049d7fb81e3a rdf:first sg:person.0711137447.78
    122 rdf:rest N541215417a864daab2b372567b30ccb5
    123 N5be4686c96234790859d27261d4fcc0b rdf:first sg:person.01240340342.20
    124 rdf:rest Nd406de7ddea94ea2bc8ad3623315a93f
    125 N733f1391e09c402c87f8f8ffd0b68c5f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    126 schema:name Tamoxifen
    127 rdf:type schema:DefinedTerm
    128 N766f5c22f6bb48e8ab90ccc594363abb schema:issueNumber 1
    129 rdf:type schema:PublicationIssue
    130 N7685235f935d4ba6808c5c0ced85f87c schema:name Springer Nature - SN SciGraph project
    131 rdf:type schema:Organization
    132 N89d3851334cf4efe9ba6475d82f299e6 rdf:first sg:person.01057073130.12
    133 rdf:rest N49f5a4e4440540eabbb9a666593e75e3
    134 N99d0f95cf8264538a89de4238f007666 schema:name dimensions_id
    135 schema:value pub.1028649218
    136 rdf:type schema:PropertyValue
    137 N9f0c66e65cc14e2bbf92e5cd15d18ec9 rdf:first sg:person.0730570317.59
    138 rdf:rest Ne22eeb4b96b749c7a867497c85e5650d
    139 N9fd3df4dbe434aa9b5a2414e95e885e0 schema:name pubmed_id
    140 schema:value 23580071
    141 rdf:type schema:PropertyValue
    142 Nb1c430a8be5b45f79cf218656b0f0d75 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    143 schema:name Cytochrome P-450 CYP2D6
    144 rdf:type schema:DefinedTerm
    145 Nb68301a32a76404fa777ccf0a2fb65b7 rdf:first sg:person.0605663452.12
    146 rdf:rest N5a20b9633bea4a82abc9049d7fb81e3a
    147 Nb7ea9905ecdb4e9dbce070f64dff887e schema:volumeNumber 139
    148 rdf:type schema:PublicationVolume
    149 Nba757868ab2a4bfe90e0649cb3b97115 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    150 schema:name Breast Neoplasms
    151 rdf:type schema:DefinedTerm
    152 Nc5f2ec5ab6df415da0b08c9eedfcd201 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    153 schema:name Middle Aged
    154 rdf:type schema:DefinedTerm
    155 Nd406de7ddea94ea2bc8ad3623315a93f rdf:first sg:person.015716462057.79
    156 rdf:rest rdf:nil
    157 Nd95d4c0ad6164df9bbe51c9248722264 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    158 schema:name Female
    159 rdf:type schema:DefinedTerm
    160 Ne22eeb4b96b749c7a867497c85e5650d rdf:first sg:person.0765260642.03
    161 rdf:rest N5be4686c96234790859d27261d4fcc0b
    162 Ne78cfa54a2164200b6bea3fb36671496 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    163 schema:name Vitamin D
    164 rdf:type schema:DefinedTerm
    165 Need515f7b34146df981e94c022f6a04e rdf:first sg:person.01261612231.85
    166 rdf:rest N9f0c66e65cc14e2bbf92e5cd15d18ec9
    167 Nf46b3380f9a54d8fb6c7ed0e094faaa4 schema:name nlm_unique_id
    168 schema:value 8111104
    169 rdf:type schema:PropertyValue
    170 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    171 schema:name Medical and Health Sciences
    172 rdf:type schema:DefinedTerm
    173 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    174 schema:name Oncology and Carcinogenesis
    175 rdf:type schema:DefinedTerm
    176 sg:journal.1092777 schema:issn 0167-6806
    177 1573-7217
    178 schema:name Breast Cancer Research and Treatment
    179 rdf:type schema:Periodical
    180 sg:person.01027032555.87 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    181 schema:familyName Perera
    182 schema:givenName Francisco E.
    183 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01027032555.87
    184 rdf:type schema:Person
    185 sg:person.01035436656.70 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    186 schema:familyName Teft
    187 schema:givenName Wendy A.
    188 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01035436656.70
    189 rdf:type schema:Person
    190 sg:person.01057073130.12 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    191 schema:familyName Vandenberg
    192 schema:givenName Theodore A.
    193 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01057073130.12
    194 rdf:type schema:Person
    195 sg:person.01061024446.05 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    196 schema:familyName Brackstone
    197 schema:givenName Muriel
    198 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01061024446.05
    199 rdf:type schema:Person
    200 sg:person.01240340342.20 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    201 schema:familyName Tirona
    202 schema:givenName Rommel G.
    203 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01240340342.20
    204 rdf:type schema:Person
    205 sg:person.01261612231.85 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    206 schema:familyName Choi
    207 schema:givenName Yun-Hee
    208 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01261612231.85
    209 rdf:type schema:Person
    210 sg:person.015716462057.79 schema:affiliation https://www.grid.ac/institutes/grid.412745.1
    211 schema:familyName Kim
    212 schema:givenName Richard B.
    213 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015716462057.79
    214 rdf:type schema:Person
    215 sg:person.0605663452.12 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    216 schema:familyName Dingle
    217 schema:givenName Brian
    218 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605663452.12
    219 rdf:type schema:Person
    220 sg:person.0711137447.78 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    221 schema:familyName Potvin
    222 schema:givenName Kylea
    223 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0711137447.78
    224 rdf:type schema:Person
    225 sg:person.0730570317.59 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    226 schema:familyName Zou
    227 schema:givenName Guangyong
    228 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0730570317.59
    229 rdf:type schema:Person
    230 sg:person.0765260642.03 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    231 schema:familyName Legan
    232 schema:givenName Robin M.
    233 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0765260642.03
    234 rdf:type schema:Person
    235 sg:person.0766401110.25 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    236 schema:familyName Gong
    237 schema:givenName Inna Y.
    238 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0766401110.25
    239 rdf:type schema:Person
    240 sg:person.0770225252.63 schema:affiliation https://www.grid.ac/institutes/grid.39381.30
    241 schema:familyName Younus
    242 schema:givenName Jawaid
    243 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0770225252.63
    244 rdf:type schema:Person
    245 sg:pub.10.1007/s00280-004-0926-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003611498
    246 https://doi.org/10.1007/s00280-004-0926-7
    247 rdf:type schema:CreativeWork
    248 sg:pub.10.1007/s00394-010-0138-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029315523
    249 https://doi.org/10.1007/s00394-010-0138-3
    250 rdf:type schema:CreativeWork
    251 sg:pub.10.1007/s10549-006-9428-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007965097
    252 https://doi.org/10.1007/s10549-006-9428-0
    253 rdf:type schema:CreativeWork
    254 sg:pub.10.1007/s10549-013-2530-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045716766
    255 https://doi.org/10.1007/s10549-013-2530-1
    256 rdf:type schema:CreativeWork
    257 sg:pub.10.1016/j.clpt.2006.03.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018855231
    258 https://doi.org/10.1016/j.clpt.2006.03.013
    259 rdf:type schema:CreativeWork
    260 sg:pub.10.1038/clpt.2011.27 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022654582
    261 https://doi.org/10.1038/clpt.2011.27
    262 rdf:type schema:CreativeWork
    263 sg:pub.10.1038/clpt.2011.32 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005561058
    264 https://doi.org/10.1038/clpt.2011.32
    265 rdf:type schema:CreativeWork
    266 sg:pub.10.1038/clpt.2011.372 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011168548
    267 https://doi.org/10.1038/clpt.2011.372
    268 rdf:type schema:CreativeWork
    269 sg:pub.10.1038/nrc2683 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032860958
    270 https://doi.org/10.1038/nrc2683
    271 rdf:type schema:CreativeWork
    272 sg:pub.10.1038/tpj.2010.28 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027819854
    273 https://doi.org/10.1038/tpj.2010.28
    274 rdf:type schema:CreativeWork
    275 sg:pub.10.1186/bcr1640 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033336327
    276 https://doi.org/10.1186/bcr1640
    277 rdf:type schema:CreativeWork
    278 sg:pub.10.1186/bcr2920 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019004438
    279 https://doi.org/10.1186/bcr2920
    280 rdf:type schema:CreativeWork
    281 https://app.dimensions.ai/details/publication/pub.1078549673 schema:CreativeWork
    282 https://doi.org/10.1001/jama.2009.1420 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044667494
    283 rdf:type schema:CreativeWork
    284 https://doi.org/10.1016/j.bcp.2012.03.017 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037122369
    285 rdf:type schema:CreativeWork
    286 https://doi.org/10.1016/s0140-6736(97)11423-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033560955
    287 rdf:type schema:CreativeWork
    288 https://doi.org/10.1016/s0169-409x(02)00066-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000686994
    289 rdf:type schema:CreativeWork
    290 https://doi.org/10.1056/nejmra032424 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024080521
    291 rdf:type schema:CreativeWork
    292 https://doi.org/10.1073/pnas.0710615105 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003974980
    293 rdf:type schema:CreativeWork
    294 https://doi.org/10.1093/aje/kwr091 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046237680
    295 rdf:type schema:CreativeWork
    296 https://doi.org/10.1093/jnci/dji005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036118248
    297 rdf:type schema:CreativeWork
    298 https://doi.org/10.1093/jnci/djs125 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035302715
    299 rdf:type schema:CreativeWork
    300 https://doi.org/10.1093/jnci/djs126 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027165104
    301 rdf:type schema:CreativeWork
    302 https://doi.org/10.1097/fpc.0b013e32833225e7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1060340765
    303 rdf:type schema:CreativeWork
    304 https://doi.org/10.1111/j.1365-2125.2010.03773.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1043371222
    305 rdf:type schema:CreativeWork
    306 https://doi.org/10.1124/dmd.110.036160 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039200983
    307 rdf:type schema:CreativeWork
    308 https://doi.org/10.1124/jpet.104.065607 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019953192
    309 rdf:type schema:CreativeWork
    310 https://doi.org/10.1124/jpet.108.149815 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000514154
    311 rdf:type schema:CreativeWork
    312 https://doi.org/10.1124/mol.51.5.741 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083087429
    313 rdf:type schema:CreativeWork
    314 https://doi.org/10.1124/mol.60.6.1399 schema:sameAs https://app.dimensions.ai/details/publication/pub.1074958474
    315 rdf:type schema:CreativeWork
    316 https://doi.org/10.1146/annurev-med-070909-182545 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013300668
    317 rdf:type schema:CreativeWork
    318 https://doi.org/10.1158/0008-5472.can-08-3933 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014845611
    319 rdf:type schema:CreativeWork
    320 https://doi.org/10.1158/1078-0432.ccr-12-2153 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052002227
    321 rdf:type schema:CreativeWork
    322 https://doi.org/10.1176/appi.ajp.2008.08040482 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063498247
    323 rdf:type schema:CreativeWork
    324 https://doi.org/10.1200/jco.2009.25.7246 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050357972
    325 rdf:type schema:CreativeWork
    326 https://doi.org/10.1200/jco.2010.31.4427 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041583874
    327 rdf:type schema:CreativeWork
    328 https://doi.org/10.1200/jco.2010.32.9839 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035143430
    329 rdf:type schema:CreativeWork
    330 https://doi.org/10.1634/theoncologist.2011-0418 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044929077
    331 rdf:type schema:CreativeWork
    332 https://www.grid.ac/institutes/grid.39381.30 schema:alternateName Western University
    333 schema:name Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada
    334 Department of Oncology, University of Western Ontario, London, ON, Canada
    335 Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada
    336 Department of Surgery, University of Western Ontario, London, ON, Canada
    337 Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, ON, Canada
    338 rdf:type schema:Organization
    339 https://www.grid.ac/institutes/grid.412745.1 schema:alternateName London Health Sciences Centre
    340 schema:name Department of Medicine, LHSC-University Hospital, Room A-LL-152, 339 Windermere Road, N6A 5A5, London, ON, Canada
    341 Department of Oncology, University of Western Ontario, London, ON, Canada
    342 Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada
    343 Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, ON, Canada
    344 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...