Evidence map›Paper›PMID 35501422›Full record

ArticleBreast cancer research and treatment2022

Single-nucleotide polymorphisms and the effectiveness of taxane-based chemotherapy in premenopausal breast cancer: a population-based cohort study in Denmark.

Cathrine F Hjorth, Per Damkier, Tore B Stage, Søren Feddersen, Stephen Hamilton-Dutoit, Mikael Rørth, Bent Ejlertsen, Timothy L Lash, Thomas P Ahern, Henrik T Sørensen and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research and treatment, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

3 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
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  3. Review
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

11 authors at 5 institutions in 2 countries.

Cathrine F HjorthDepartment of Clinical Medicine and Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus University, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark. cfh@clin.au.dk.ORCID http://orcid.org/0000-0003-4378-8531
Per DamkierDepartment of Clinical Pharmacology, Odense University Hospital, Odense, Denmark.
Tore B StageClinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark Odense, Odense, Denmark.
Søren FeddersenDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark.
Stephen Hamilton-DutoitDepartment of Pathology, Aarhus University Hospital, Aarhus N, Denmark.
Mikael RørthDepartment of Clinical Medicine and Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus University, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
Bent EjlertsenDepartment of Oncology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark.
Timothy L LashDepartment of Clinical Medicine and Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus University, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
Thomas P AhernDepartment of Surgery, The Robert Larner, M.D. College of Medicine, The University of Vermont, Burlington, VT, USA.
Henrik T SørensenDepartment of Clinical Medicine and Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus University, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
Deirdre Cronin-FentonDepartment of Clinical Medicine and Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus University, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
Aarhus University Hospital · DKUniversity of Southern Denmark · DKCopenhagen University Hospital · DKEmory University · USUniversity of Vermont · US

Funding

Dansk Kræftforsknings Fond PLESNER-FAST-Active.FID1839672Kræftens Bekæmpelse R167-A11045-17-S2Lundbeckfonden R167-2013-15861US National Cancer Institute R01CA16682
6 · The paper itself

Abstract

purposeTaxane-based chemotherapy is the primary treatment for premenopausal breast cancer. Although being inconsistent, research suggests that variant alleles alter pharmacokinetics through reduced function of OATP transporters (limiting hepatic uptake), CYP-450 enzymes (hampering drug metabolism), and ABC transporters (decreasing clearance). Reduced function of DNA repair enzymes may hamper effectiveness through dose-limiting toxicities. We investigated whether single-nucleotide polymorphisms (SNPs) were associated with breast cancer recurrence or mortality in premenopausal women diagnosed with breast cancer.

methodsWe conducted a population-based cohort study of premenopausal women diagnosed with non-distant metastatic breast cancer in Denmark during 2007‒2011, when guidelines recommended adjuvant combination chemotherapy (taxanes, anthracyclines, and cyclophosphamide). Using archived formalin-fixed paraffin-embedded primary tumor tissue, we genotyped 26 SNPs using TaqMan assays. Danish health registries provided data on breast cancer recurrence (through September 25, 2017) and death (through December 31, 2019). We fit Cox regression models to calculate crude hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and mortality across genotypes.

resultsAmong 2,262 women, 249 experienced recurrence (cumulative incidence: 13%) and 259 died (cumulative incidence: 16%) during follow-up (median 7.0 and 10.1 years, respectively). Mortality was increased in variant carriers of GSTP1 rs1138272 (HR: 1.30, 95% CI 0.95-1.78) and CYP3A rs10273424 (HR: 1.33, 95% CI 0.98-1.81). SLCO1B1 rs2306283 (encoding OATP1B1) variant carriers had decreased recurrence (HR: 0.82, 95% CI 0.64-1.07) and mortality (HR: 0.77, 95% CI 0.60-0.98).

conclusionDocetaxel effectiveness was influenced by SNPs in GSTP1, CYP3A, and SLCO1B1 in premenopausal women with non-distant metastatic breast cancer, likely related to altered docetaxel pharmacokinetics. These SNPs may help determine individual benefit from taxane-based chemotherapy.

Indexed as

Breast NeoplasmsBridged-Ring CompoundsChemotherapy, AdjuvantCohort StudiesCytochrome P-450 CYP3ADenmarkDocetaxelFemaleHumansLiver-Specific Organic Anion Transporter 1Neoplasm Recurrence, LocalPolymorphism, Single NucleotideTaxoidsBridged-Ring CompoundsCytochrome P-450 CYP3ADocetaxelLiver-Specific Organic Anion Transporter 1SLCO1B1 protein, humantaxaneTaxoidsBreast neoplasmMortalityNeoplasm recurrenceSingle-nucleotide polymorphismsTaxanes

Identifiers

PMID35501422
PMCPMC9239972
OpenAlexW4225287735

What OpenQuestion holds

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LicenceCC BY
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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.