Evidence map›Paper›PMID 40452016›Full record

ArticleBMC cancer2025

Clinical and pharmacogenomic predictors of survival in tamoxifen treated breast cancer female patients: a real-world study.

Abdullah R Al-Matrafi, Khaled F Bedair, Sundararajan Srinivasan, Colin Palmer, Archie Campbell, Caroline Hayward, Ewan R Pearson, Russell D Petty

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Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Abdullah R Al-MatrafiPopulation Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.
Khaled F BedairPopulation Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.
Sundararajan SrinivasanPopulation Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.
Colin PalmerPopulation Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.
Archie CampbellCentre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
Caroline HaywardMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
Ewan R PearsonPopulation Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.
Russell D PettyMolecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK. r.petty@dundee.ac.uk.

Funding

Wellcome Trust
6 · The paper itself

Abstract

aimTo investigate the impact of tamoxifen dose, CYP2D6 inhibitors, CYP2D6*4 genotype, and non-genetic parameters on the outcomes of tamoxifen treated female breast cancer patients.

methodWe retrospectively included 3218 female patients who initiated tamoxifen following a diagnosis of breast cancer with long-term follow-up (median 7.5 years). A subgroup analysis of 303 genotyped patients with a median follow-up of 9.7 years was also conducted. The outcomes of interest were overall survival (OS) and breast-cancer-specific survival (BCS).

resultsIn the whole cohort, an additional 20 mg of tamoxifen during six-month duration was associated with a 1.6% reduction in all-cause mortality (HR: 0.984, 95% CI: 0.982-0.985, P < 0.001) and a 1.9% decrease in breast cancer mortality (HR: 0.981, 95% CI: 0.979-0.984, P < 0.001). In the genotyped subgroup, CYP2D6*4 heterozygotes had a 76% greater risk of all-cause mortality than *4 non-carriers (HR: 1.76, 95% CI: 1.07-2.9, P = 0.025). For breast cancer-specific mortality, CYP2D6*4 heterozygotes and homozygotes had increased risk by 3.7-fold (HR: 3.7, 95% CI: 1.32-10.6, P = 0.01) and 11.6-fold (HR: 11.6, 95% CI: 1.3-103.5, P = 0.03), respectively.

conclusionOur study demonstrates that carriers of CYP2D6*4 have a higher risk of both all-cause and breast cancer-specific mortality and indicates that longer follow-up time may be crucial to determining impact. The shorter follow-up in previous studies may be a key reason for the conflicting results. A large real-world pharmacogenomic study with long-term follow-up is warranted to determine the impact of CYP2D6 genotyping and its implications for clinical decision making.

Indexed as

Antineoplastic Agents, HormonalBreast NeoplasmsCytochrome P-450 CYP2D6TamoxifenAdultAgedCytochrome P-450 CYP2D6 InhibitorsFemaleFollow-Up StudiesGenotypeHumansMiddle AgedPharmacogeneticsPrognosisRetrospective StudiesAntineoplastic Agents, HormonalCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsTamoxifenBreast CancerCYP2D6CYP2D6*4CYP2D6 inhibitorsGermlinePharmacogenomicsReal-worldSSRIsSurvivalTamoxifen

Identifiers

PMID40452016
PMCPMC12128510

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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.