Evidence map›Paper›PMID 37042388›Full record

ArticleClinical pharmacology and therapeutics2023

Effects of Genetic Polymorphisms of Drug Metabolizing Enzymes and co-Medications on Tamoxifen Metabolism in Black South African Women with Breast Cancer.

Shingirai M Chiwambutsa, Oluwatosin Ayeni, Nyasha Kapungu, Comfort Kanji, Roslyn Thelingwani, Wenlong Carl Chen, Dikeledi H Mokone, Daniel S O'Neil, Alfred I Neugut, Judith S Jacobson and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical pharmacology and therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.0field-weighted citation impact, top 16% of its field
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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Genetic Variation inJournal of personalized medicine · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 3 countries.

Shingirai M ChiwambutsaSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Oluwatosin AyeniStrengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Nyasha KapunguAfrican Institute of Biomedical Science and Technology (AiBST), Harare, Zimbabwe.ORCID 0000-0002-3252-8753
Comfort KanjiAfrican Institute of Biomedical Science and Technology (AiBST), Harare, Zimbabwe.ORCID 0000-0002-5278-0614
Roslyn ThelingwaniAfrican Institute of Biomedical Science and Technology (AiBST), Harare, Zimbabwe.ORCID 0000-0001-8396-6609
Wenlong Carl ChenSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Dikeledi H MokoneDepartment of Surgery, Sefako Makgatho Health Sciences University, Dr George Mukhari Academic Hospital, Ga-Rankuwa, South Africa.ORCID 0000-0002-1957-4165
Daniel S O'NeilComprehensive Cancer Center and Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Alfred I NeugutDepartment of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Judith S JacobsonHerbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Paul RuffStrengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Herbert CubaschStrengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Maureen JoffeStrengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID 0000-0001-8616-9672
Collen MasimirembwaSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
African Institute of Biomedical Science and Technology · ZWSouth African Medical Research Council · ZAColumbia University · USNational Health Laboratory Service · ZAUniversity of the Witwatersrand · ZASefako Makgatho Health Sciences University · ZAUniversity of Miami · US

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
Novel predictors of survival among breast cancer patients with/without HIV in South AfricaR01CA250012 · NCI · WITS HEALTH CONSORTIUM (PTY), LTD · PI CUBASCH, HERBERT, EL-SADR, WAFAA M. · 2020 to 2024
$2.0M
HIV's Effects on Breast Cancer Treatment and Outcomes in South AfricaR01CA192627 · NCI · WITS HEALTH CONSORTIUM (PTY), LTD · PI JACOBSON, JUDITH S, JOFFE, MAUREEN · 2015 to 2019
$1.7M
NCI NIH HHS P30 CA013696NCI NIH HHS R01 CA192627NCI NIH HHS R01 CA250012
6 · The paper itself

Abstract

Clinical outcomes of tamoxifen (TAM) treatment show wide interindividual variability. Comedications and genetic polymorphisms of enzymes involved in TAM metabolism contributes to this variability. Drug-drug and drug-gene interactions have seldom been studied in African Black populations. We evaluated the effects of commonly co-administered medicines on TAM pharmacokinetics in a cohort of 229 South African Black female patients with hormone-receptor positive breast cancer. We also investigated the pharmacokinetic effects of genetic polymorphism in enzymes involved in TAM metabolism, including the variants CYP2D6*17 and *29, which have been mainly reported in people of African descent. TAM and its major metabolites, N-desmethyltamoxifen (NDM), 4-OH-tamoxifen, and endoxifen (ENDO), were quantified in plasma using the liquid chromatography-mass spectrometry. The GenoPharm open array was used to genotype CYP2D6, CYP3A5, CYP3A4, CYP2B6, CYP2C9, and CYP2C19. Results showed that CYP2D6 diplotype and CYP2D6 phenotype significantly affected endoxifen concentration (P < 0.001 and P < 0.001). CYP2D6*17 and CYP2D6*29 significantly reduced the metabolism of NDM to ENDO. Antiretroviral therapy had a significant effect on NDM levels and the TAM/NDM and NDM/ENDO metabolic ratios but did not result in significant effects on ENDO levels. In conclusion, CYP2D6 polymorphisms affected endoxifen concentration and the variants CYP2D6*17 and CYP2D6*29 significantly contributed to low exposure levels of ENDO. This study also suggests a low risk of drug-drug interaction in patients with breast cancer on TAM.

Indexed as

Cytochrome P-450 CYP2D6NeoplasmsAntineoplastic Agents, HormonalFemaleGenotypeHumansPolymorphism, GeneticSouth AfricaTamoxifen4-hydroxy-N-desmethyltamoxifenAntineoplastic Agents, HormonalCytochrome P-450 CYP2D6N-desmethyltamoxifenTamoxifen

Identifiers

PMID37042388
PMCPMC11016593
OpenAlexW4365135646

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.