Evidence map›Paper›PMID 24060820›Full record

SynthesisClinical pharmacology and therapeutics2014

CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.

M A Province, M P Goetz, H Brauch, D A Flockhart, J M Hebert, R Whaley, V J Suman, W Schroth, S Winter, H Zembutsu and 45 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Clinical pharmacology and therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 6 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. CYP2D6 Phenotype and Breast Cancer Outcomes: A Bias Analysis and Meta-Analysis.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Guideline
  5. Guideline
  6. Polymorphism at 19q13.41 Predicts Breast Cancer Survival Specifically after Endocrine Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015
    Pooled it
  7. Trial
  8. Trial
  9. Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020
    Trial
  10. Trial
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

55 authors.

M A ProvinceCenter for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
M P GoetzDepartment of Oncology and Pharmacology, Mayo Clinic, Rochester, Minnesota, USA.
H BrauchDr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University, Tuebingen, Germany.
D A FlockhartDivision of Clinical Pharmacology, School of Medicine, Indiana University, Bloomington, Indiana, USA.
J M HebertDepartment of Genetics, School of Medicine, Stanford University, Stanford, California, USA.
R WhaleyDepartment of Genetics, School of Medicine, Stanford University, Stanford, California, USA.
V J SumanDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
W SchrothDr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University, Tuebingen, Germany.
S WinterDr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University, Tuebingen, Germany.
H ZembutsuLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
T MushirodaLaboratory for Pharmacogenetics, RIKEN Center for Genomic Medicine, Yokohama, Japan.
W G NewmanCentre for Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
M-T M LeeLaboratory for International Alliance, RIKEN Center for Genomic Medicine, Yokohama, Japan.
C B AmbrosoneDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, USA.
M W BeckmannDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
J-Y ChoiDepartment of Biomedical Science, Graduate School, Seoul National University, Seoul, Korea.
A-S DieudonnéDepartment of Oncology, Catholic University Leuven, Leuven, Belgium.
P A Fasching1] Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany [2] Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
R FerraldeschiCentre for Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
L GongDepartment of Genetics, School of Medicine, Stanford University, Stanford, California, USA.
E Haschke-BecherUniversity Institute of Medical and Chemical Laboratory Diagnostics, Paracelsus Private Medical University, Salzburg, Austria.
A HowellThe Christie NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
L B JordanDepartment of Pathology, Ninewells Hospital and Medical School, Dundee, UK.
U HamannMolecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
K KiyotaniLaboratory for Pharmacogenetics, RIKEN Center for Genomic Medicine, Yokohama, Japan.
P KripplMedical University Graz, Graz, Austria.
D LambrechtsVesalius Research Center, VIB and Laboratory of Translational Genetics, Department of Oncology, Catholic University Leuven, Leuven, Belgium.
A LatifCentre for Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
U LangsenlehnerMedical University Graz, Graz, Austria.
W LorizioDivision of General Internal Medicine, Department of Medicine and Clinical Pharmacology and Experimental Therapeutics, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
P NevenDepartment of Gynecology and Obstetrics, University Hospitals Leuven, Leuven, Belgium.
A T NguyenDivision of Clinical Pharmacology, School of Medicine, Indiana University, Bloomington, Indiana, USA.
B-W ParkDepartment of Surgery, Yonsei University Health System, Seoul, Korea.
C A PurdieDepartment of Pathology, Ninewells Hospital and Medical School, Dundee, UK.
P QuinlanDundee Cancer Centre, Dundee, UK.
W RennerMedical University Graz, Graz, Austria.
M Schmidt1] Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University, Tuebingen, Germany [2] Department of Gynecology and Obstetrics, University of Mainz, Mainz, Germany.
M SchwabDepartment of Clinical Pharmacology and Toxicology, University Hospital Tuebingen, Tuebingen, Germany.
J-G Shin1] Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan, Korea [2] Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Korea.
J C StinglDivision of Research, Federal Institute for Drugs and Medical Devices, University of Bonn Medical Faculty, Bonn, Germany.
P WegmanDepartment of Clinical Medicine, Ö rebro University, Örebro, Sweden.
S WingrenDepartment of Clinical Medicine, Ö rebro University, Örebro, Sweden.
A H B WuDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA.
E ZivDivision of General Internal Medicine, Department of Medicine and Clinical Pharmacology and Experimental Therapeutics, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
G ZirpoliDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, USA.
A M ThompsonDundee Cancer Centre, Dundee, UK.
V C JordanDepartment of Oncology, Georgetown University, Washington, DC, USA.
Y NakamuraLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
R B Altman1] Department of Genetics, School of Medicine, Stanford University, Stanford, California, USA [2] Department of Bioengineering, Stanford University, Stanford, California, USA.
M M AmesDepartment of Pharmacology, Mayo Clinic, Rochester, Minnesota, USA.
R M WeinshilboumDepartment of Pharmacology, Mayo Clinic, Rochester, Minnesota, USA.
M EichelbaumDr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University, Tuebingen, Germany.
J N IngleDepartment of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
T E KleinDepartment of Genetics, School of Medicine, Stanford University, Stanford, California, USA.
International Tamoxifen Pharmacogenomics Consortium

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
TRANSLATIONAL RESEARCHU10CA025224 · NCI · MAYO CLINIC ROCHESTER · PI BUCKNER, JAN C · 1985 to 2013
$85.0M
Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI STEPHEN W BYERS · 1990 to 2026
$71.5M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9M
SUPPLEMENTU10CA037404 · NCI · MAYO CLINIC ROCHESTER · PI LOPRINZI, CHARLES L · 1985 to 2014
$34.8M
Tissue and Outcomes CoreP50CA058207 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRAY, JOE W. · 1992 to 2012
$32.7M
PharmGKB: pharmacogenomics knowledge for precision medicineR24GM061374 · NIGMS · STANFORD UNIVERSITY · PI ALTMAN, RUSS BIAGIO, KLEIN, TERI ELLEN · 2010 to 2018
$25.2M
Pharmacogenetics of Phase II Drug Metabolizing EnzymesU19GM061388 · NIGMS · MAYO CLINIC ROCHESTER · PI WEINSHILBOUM, RICHARD M. · 2010 to 2014
$15.8M
SIOUX COMMUNITY CANCER CONSORTIUMU10CA035103 · NCI · UNIVERSITY OF SOUTH DAKOTA · PI MAZURCZAK, MIROSLAW · 1985 to 2014
$11.6M
MISSOURI VALLEY CANCER CONSORTIUM CCOPU10CA063849 · NCI · MISSOURI VALLEY CANCER CONSORTIUM, INC. · PI SOORI, GAMINI · 1994 to 2014
$11.3M
COMMUNITY CLINICAL ONCOLOGY PROGRAMU10CA035195 · NCI · CARLE FOUNDATION HOSPITAL (URBANA, IL) · PI ROWLAND, KENDRITH MARTIN · 1985 to 2014
$11.3M
Illinois Oncology Research Association Community Clinical Oncology ProgramU10CA035113 · NCI · ONCOLOGY-HEMATOLOGY ASSOC-CENTRAL ILL · PI LE-LINDQWISTER, NGUYET A. · 1985 to 2014
$10.8M
Cancer Research UKNCI NIH HHS 1R01CA133049-01NCI NIH HHS CA051008NCI NIH HHS CA-116201NCI NIH HHS CA-15083NCI NIH HHS CA-25224NCI NIH HHS CA-35101NCI NIH HHS CA35103NCI NIH HHS CA-35113NCI NIH HHS CA-35195NCI NIH HHS CA-35269NCI NIH HHS CA-35272NCI NIH HHS CA-35415NCI NIH HHS CA-35448NCI NIH HHS CA-37404NCI NIH HHS CA-37417NCI NIH HHS CA-51008NCI NIH HHS CA-52352NCI NIH HHS CA-58207NCI NIH HHS CA-60274NCI NIH HHS CA-63849NCI NIH HHS N01 CA015083NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA051008NCI NIH HHS P50 CA058207NCI NIH HHS P50 CA116201NCI NIH HHS R01 CA132780NCI NIH HHS R01 CA133049NCI NIH HHS U10 CA025224NCI NIH HHS U10 CA035101NCI NIH HHS U10 CA035103NCI NIH HHS U10 CA035195NCI NIH HHS U10 CA035269NCI NIH HHS U10 CA035272NCI NIH HHS U10 CA035415NCI NIH HHS U10 CA035448NCI NIH HHS U10 CA037404NCI NIH HHS U10 CA037417NCI NIH HHS U10 CA063849NIGMS NIH HHS R24 GM061374NIGMS NIH HHS R24 GM61374NIGMS NIH HHS T32 GM007546NIGMS NIH HHS U19 GM061388NIGMS NIH HHS U19 GM61388
6 · The paper itself

Abstract

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.

Indexed as

AgedAntineoplastic Agents, HormonalBreast NeoplasmsCytochrome P-450 CYP2D6FemaleGenetic VariationGenotypeHumansMenopauseMiddle AgedPharmacogeneticsSurvival AnalysisTamoxifenTreatment OutcomeAntineoplastic Agents, HormonalCytochrome P-450 CYP2D6Tamoxifen

Identifiers

PMID24060820
PMCPMC3904554

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.