Evidence map›Paper›PMID 21430657›Full record

ArticleClinical pharmacology and therapeutics2011

Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes.

L Madlensky, L Natarajan, S Tchu, M Pu, J Mortimer, S W Flatt, D M Nikoloff, G Hillman, M R Fontecha, H J Lawrence and 3 more

4 registry-linked trialsOpen access · greenAbstract readComparative StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacology and therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 148 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
148citing papers in PubMed, 4 pooled it
17.6field-weighted citation impact, top 1% 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.

NCT00003787 completednot on this map

Dietary Intervention in Women Who Have Been Treated For Stage I, Stage II, or Stage III Breast Cancer: Women's Healthy Eating and Living (WHEL) Study

TypeobservationalSponsorUniversity of California, San DiegoRan1995 to 2018Enrolled3,088ConditionsBreast CancerArmseducational/counseling intervention, therapeutic dietary intervention
NCT03504631 unknown statusnot on this mapstarted 2017, after this paper: background citation

Genotyping and Phenotyping of CYP2D6 as Predictor of Z-endoxifen Plasma Levels in Breast Cancer Patients on Tamoxifen Treatment

TypeobservationalSponsorTrisakti UniversityRan2017 to 2018Enrolled117ConditionsBreast Cancer FemaleArmsNo intervention
NCT04312347 nacompletednot on this mapstarted 2019, after this paper: background citation

Tamoxifen Dose Adjustment on ER+ Breast Cancer Patients Based on Genomic and Metabolite Concentrations Analysis

TypeinterventionalSponsorNalagenetics Pte LtdRan2019 to 2021Enrolled151ConditionsER+ Breast CancerArmsTamoxifen dose adjustment
NCT05133674 phase2unknown statusnot on this mapstarted 2022, after this paper: background citation

Therapeutic Dose Monitoring (TDM) of Tamoxifen and Its Active Metabolites in Combination With Patient-reported Symptom Scores Among Patients With Breast Cancer Receiving Adjuvant Tamoxifen Treatment

TypeinterventionalSponsorKarolinska University HospitalRan2022 to 2023Enrolled40ConditionsBreast Cancer, Breast Carcinoma, Breast Tumors, Cancer of BreastArmsTamoxifen 20 mg
3 · Its place in the literature

Who cites it

148 citing papers in PubMed, 4 syntheses or guidelines pooled it, 328 citations in OpenAlex.

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  12. Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020
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  18. CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013
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88 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 1 country.

L MadlenskyCancer Prevention and Control Program, Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California, USA.
L Natarajan
S Tchu
M Pu
J Mortimer
S W Flatt
D M Nikoloff
G Hillman
M R Fontecha
H J Lawrence
B A Parker
A H B Wu
J P Pierce
University of California, San Diego · USMaterials Systems (United States) · USUniversity of California, San Francisco · USCity Of Hope National Medical Center · US

Funding

ZOVIRAX CREAM TO TREAT HERPES LABIALIS IN ADOLESCENTSM01RR000827 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHANG, R JEFFREY · 1985 to 2010
$74.3M
XOLAIR IN SUBJECTS WITH MODERATE TO SEVERE ATOPIC DERMATITIS WITH FOOD ALLERGYM01RR000070 · NCRR · STANFORD UNIVERSITY · PI RASGON, NATALIE L · 1985 to 2008
$32.4M
ZD1839 FOR MALIGNANT ASTROCYTOMA OR GLIOBLASTOMA AND MENINGIOMAM01RR000079 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KESSLER, DAVID A · 1985 to 2006
$26.0M
RCT OF PLANT-BASED DIET IN BREAST CANCER RECURRENCER01CA069375 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PIERCE, JOHN P · 1998 to 2007
$25.5M
NCI NIH HHS CA 69375NCI NIH HHS R01 CA069375NCRR NIH HHS M01 RR000070NCRR NIH HHS M01 RR000079NCRR NIH HHS M01-RR00070NCRR NIH HHS M01-RR00079NCRR NIH HHS M01 RR000827NCRR NIH HHS M01-RR00827
6 · The paper itself

Abstract

We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen and examined potential correlates of endoxifen concentration levels in serum including cytochrome P450 2D6 (CYP2D6) metabolizer phenotype and body mass index (BMI). Concentration levels of tamoxifen, endoxifen, 4-hydroxytamoxifen (4OH-tamoxifen), and N-desmethyltamoxifen (ND-tamoxifen) were measured from samples taken from 1,370 patients with estrogen receptor (ER)-positive breast cancer who were participating in the Women's Healthy Eating and Living (WHEL) Study. We tested these concentration levels for possible associations with breast cancer outcomes and found that breast cancer outcomes were not associated with the concentration levels of tamoxifen, 4-hydroxytamoxifen, and ND-tamoxifen. For endoxifen, a threshold was identified, with women in the upper four quintiles of endoxifen concentration appearing to have a 26% lower recurrence rate than women in the bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55-1.00)). The predictors of this higher-risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and lower tamoxifen concentrations as compared with the mean for the cohort as a whole. This study suggests that there is a minimal concentration threshold above which endoxifen is effective against the recurrence of breast cancer and that ~80% of tamoxifen takers attain this threshold.

Indexed as

Breast NeoplasmsCohort StudiesCytochrome P-450 CYP2D6FemaleGenotypeHumansMiddle AgedPhenotypeTamoxifenTreatment Outcome4-hydroxy-N-desmethyltamoxifenCytochrome P-450 CYP2D6Tamoxifen

Identifiers

PMID21430657
PMCPMC3081375
OpenAlexW2135502243

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.