Evidence map›Paper›PMID 41636472›Full record

ArticleBritish journal of clinical pharmacology2026

Pharmacogenetic CYP2B6 variants affect steroid hormone metabolism in human breast cancer cells.

Marco Hoffmann, Julian Peter Müller, Stefan Düsterhöft, Sabrina Yamoune, Katja Susanne Just, Julia Carolin Stingl

Abstract read
In one paragraph

Article in British journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

What it found

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. 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

6 authors.

Marco HoffmannInstitute of Clinical Pharmacology, University Hospital RWTH Aachen, Aachen, Germany.ORCID https://orcid.org/0009-0001-0447-548X
Julian Peter MüllerInstitute of Clinical Pharmacology, University Hospital RWTH Aachen, Aachen, Germany.ORCID https://orcid.org/0009-0002-1505-5664
Stefan DüsterhöftInstitute of Molecular Pharmacology, University Hospital RWTH Aachen, Aachen, Germany.
Sabrina YamouneInstitute of Clinical Pharmacology, University Hospital RWTH Aachen, Aachen, Germany.
Katja Susanne JustInstitute of Clinical Pharmacology, University Hospital RWTH Aachen, Aachen, Germany.ORCID https://orcid.org/0000-0002-6782-8078
Julia Carolin StinglInstitute of Clinical Pharmacology, University Hospital RWTH Aachen, Aachen, Germany.

Funding

Deutsche Forschungsgemeinschaft 455749974EraPerMed project Artipro by the German Ministery of Research and Education 01KU2212
6 · The paper itself

Abstract

aimsCYP2B6 is a key enzyme involved in the metabolism of steroid hormones such as testosterone and estradiol. Common genetic CYP2B6 variants (*4, *5, *6, *9) are associated with reduced enzymatic activity and have been linked to increased breast cancer risk and poor prognosis. However, the impact of these genetic variants on testosterone and estradiol metabolism in humans is not understood. Therefore, this study aimed to investigate how these pharmacogenetic CYP2B6 variants affect metabolism of these steroid hormones in a human breast cancer model and how this may contribute to altered steroid hormone profiles in breast cancer.

methodsT47D breast cancer cells were engineered to stably overexpress CYP2B6 wild type and the variants *4, *5, *6 and *9 using a retroviral pMOWS vector system. The metabolites 16α-/16β-hydroxytestosterone and 2-/4-hydroxyestradiol were analysed using HPLC-MS/MS after incubation of testosterone or estradiol with CYP2B6 and CYP1B1 supersomes and the modified T47D cells. Conversion of testosterone metabolites to oestrogens by aromatase was also tested.

resultsCYP2B6 supersomes predominantly formed 16β-hydroxytestosterone and 2-hydroxyestradiol, while CYP1B1 predominantly produced 16α-hydroxytestosterone and 4-hydroxyestradiol. CYP2B6*6 overexpression in T47D increased 16α-hydroxytestosterone formation, while *4 and 9 showed decreased metabolism compared to wild type. CYP2B6*5 produced reduced 16β-hydroxytestosterone levels. Aromatase converts 16α-metabolite to estriol and 16β-hydroxytestosterone to 16-epiestriol.

conclusionsThis study demonstrates that common CYP2B6 variants alter testosterone metabolism in a human breast cancer model, potentially disrupting steroid hormone balance and contributing to a tumour-promoting environment. These findings highlight the potential relevance of pharmacogenetic profiling in breast cancer risk assessment.

Indexed as

Breast NeoplasmsCytochrome P-450 CYP2B6EstradiolPharmacogenomic VariantsTestosteroneAromataseCell Line, TumorCytochrome P-450 CYP1B1FemaleHumansHydroxytestosteronesTandem Mass SpectrometryAromataseCYP1B1 protein, humanCYP2B6 protein, humanCytochrome P-450 CYP1B1Cytochrome P-450 CYP2B6EstradiolHydroxytestosteronesTestosteronebreast cancerCYP2B6drug metabolizing enzymesgender‐sensitive pharmacologypharmacogeneticssteroid metabolism

Identifiers

PMID41636472
PMCPMC13304254

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LicenceCC BY
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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.