Evidence map›Paper›PMID 32813313›Full record

ArticlePharmacology research & perspectives2020

Predicting steady-state endoxifen plasma concentrations in breast cancer patients by CYP2D6 genotyping or phenotyping. Which approach is more reliable?

Milena Gusella, Felice Pasini, Barbara Corso, Laura Bertolaso, Giovanni De Rosa, Cristina Falci, Yasmina Modena, Carmen Barile, Donatella Da Corte Z, AnnaPaola Fraccon and 9 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in Pharmacology research & perspectives, 2020. 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
0.9field-weighted citation impact, top 25% 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, 7 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. ClinicalCancers · 2021
    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

19 authors at 8 institutions in 1 country.

Milena GusellaOncology Unit, AULSS5 Polesana, Rovigo, Italy.ORCID 0000-0002-6257-0282
Felice PasiniOncology Unit, Casa di Cura Pederzoli, Peschiera del Garda, Italy.
Barbara CorsoNational Research Council, Neuroscience Institute, Padova, Italy.ORCID 0000-0002-0684-9078
Laura BertolasoOncology Unit, AULSS5 Polesana, Rovigo, Italy.
Giovanni De RosaClinical Pharmacology Unit of the Department of Medicine (DIMED), University of Padova, Padova, Italy.
Cristina FalciOncology Unit 2, Istituto Oncologico Veneto (IOV), IRCCS Padova, Padova, Italy.
Yasmina ModenaOncology Unit, AULSS5 Polesana, Rovigo, Italy.
Carmen BarileOncology Unit, AULSS5 Polesana, Rovigo, Italy.
Donatella Da Corte ZOncology Unit, Ospedale di Belluno, Belluno, Italy.
AnnaPaola FracconOncology Unit, Casa di Cura Pederzoli, Peschiera del Garda, Italy.
Silvia TosoOncology Unit, Ospedale di Adria, Polesana, Italy.
Elisabetta CretellaOncology Unit, Ospedale di Bolzano, Bolzano, Italy.
Antonella BrunelloOncology Unit 1, Istituto Oncologico Veneto (IOV), IRCCS Padova, Padova, Italy.
Caterina ModonesiOncology Unit, Ospedali Riuniti Padova Sud, Padova, Italy.
Romana SegatiOncology Unit, Ospedale di Feltre, Feltre, Italy.
Cristina OlianiOncology Unit, AULSS5 Polesana, Rovigo, Italy.
Nadia MinicuciNational Research Council, Neuroscience Institute, Padova, Italy.
Roberto PadriniClinical Pharmacology Unit of the Department of Medicine (DIMED), University of Padova, Padova, Italy.
Italian TAM Group
Polo d’Innovazione di Genomica · ITUniversity of Padua · ITCasa di Cura Villa Garda · ITIstituto Oncologico Veneto · ITNeuroscience Institute · ITOspedale Civile di Giaveno · ITOspedale di Belcolle · ITOspedale di Bolzano · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In previous studies, steady-state Z-endoxifen plasma concentrations (ENDOss) correlated with relapse-free survival in women on tamoxifen (TAM) treatment for breast cancer. ENDOss also correlated significantly with CYP2D6 genotype (activity score) and CYP2D6 phenotype (dextromethorphan test). Our aim was to ascertain which method for assessing CYP2D6 activity is more reliable in predicting ENDOss. The study concerned 203 Caucasian women on tamoxifen-adjuvant therapy (20 mg q.d.). Before starting treatment, CYP2D6 was genotyped (and activity scores computed), and the urinary log(dextromethorphan/dextrorphan) ratio [log(DM/DX)] was calculated after 15 mg of oral dextromethorphan. Plasma concentrations of TAM, N-desmethyl-tamoxifen (ND-TAM), Z-4OH-tamoxifen (4OH-TAM) and ENDO were assayed 1, 4, and 8 months after first administering TAM. Multivariable regression analysis was used to identify the clinical and laboratory variables predicting log-transformed ENDOss (log-ENDOss). Genotype-derived CYP2D6 phenotypes (PM, IM, NM, EM) and log(DM/DX) correlated independently with log-ENDOss. Genotype-phenotype concordance was almost complete only for poor metabolizers, whereas it emerged that 34% of intermediate, normal, and ultrarapid metabolizers were classified differently based on log(DM/DX). Multivariable regression analysis selected log(DM/DX) as the best predictor, with patients' age, weak inhibitor use, and CYP2D6 phenotype decreasingly important: log-ENDOss = 0.162 - log(DM/DX) × 0.170 + age × 0.0063 - weak inhibitor use × 0.250 + IM × 0.105 + (NM + UM) × 0.210; (R

Indexed as

Administration, OralAdultAgedAged, 80 and overBreast NeoplasmsChemotherapy, AdjuvantCytochrome P-450 CYP2D6DextromethorphanFemaleGenotyping TechniquesHumansMiddle AgedTamoxifen4-hydroxy-N-desmethyltamoxifenCytochrome P-450 CYP2D6DextromethorphanN-desmethyltamoxifenTamoxifenbreast cancerCYP2D6dextromethorphanendoxifen

Identifiers

PMID32813313
PMCPMC7437348
OpenAlexW3081362610

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.