Evidence map›Paper›PMID 25287073›Full record

ArticleThe pharmacogenomics journal2015

Genetic variants of kinase suppressors of Ras (KSR1) to predict survival in patients with ERα-positive advanced breast cancer.

L Benhaim, W Zhang, T Wakatsuki, D Yang, A Gerger, P Bohanes, D Paez, F Loupakis, M J LaBonte, Y Ning and 7 more

Abstract read
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In one paragraph

Article in The pharmacogenomics journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact, top 90% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. 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

17 authors at 4 institutions in 3 countries.

L Benhaim1] University of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA [2] UMRS-775 "Bases moléculaires de la réponse aux xénobiotiques", University Paris Descartes, Paris, France.
W ZhangUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
T WakatsukiUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
D YangUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
A GergerUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
P BohanesUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
D PaezUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
F LoupakisUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
M J LaBonteUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
Y NingUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
R El-KhoueiryUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
R LadnerUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
P WilsonUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
H ZhangDepartment of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
G GiamasDepartment of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
J StebbingDepartment of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
H J LenzUniversity of Southern California Norris Comprehensive Cancer Center, Division of Medical Oncology, Los Angeles, CA, USA.
University of Southern California · USUSC Norris Comprehensive Cancer Center · USImperial College London · GBHammersmith Hospital · GB

Funding

Cancer Research UK 14549Department of Health NIHR-RP-011-053Medical Research Council MR/L000172/1
6 · The paper itself

Abstract

In patients with breast cancer (BC), deregulation of estrogen receptor (ERα) activity may account for most resistance to endocrine therapies. Our previous study used a whole-human kinome siRNA screen to identify functional actors in ERα modulation and showed the implication of proteins kinase suppressors of ras (KSR1). From those findings we evaluated the clinical impact of KSR1 variants in patients with ERα+ BC treated with TAM. DNA was obtained from 222 patients with advanced ERα+ BC treated with TAM who had undergone surgery from 1981 to 2003. We selected three potentially functional relevant KSR1 polymorphisms; two within the 3'UTR (rs224190, rs1075952) and one in the coding exon 7 (rs2293180). The primary end points were overall survival (OS) and disease-free survival (DFS). After a 6.4-year median follow-up, patients carrying the rs2241906 TT genotype showed shorter DFS (2.1 vs 7.1 years, P=0.005) and OS (2.6 vs 8.4 years P=0.002) than those with the TC or TT genotypes. Those associations remained significant in the multivariable analysis adjusting age, lymph node status, LMTK3 and IGFR variants and HER2 status. The polymorphisms rs2241906 and rs1075952 were in linkage disequilibrium. No association was shown between rs2293180 and survival. Among the actors of ERα signaling, KSR1 rs2241906 variants may predict survival in patients with advanced ERα+ BC treated with adjuvant TAM.

Indexed as

3' Untranslated RegionsAdultAgedAged, 80 and overBreast NeoplasmsDisease-Free SurvivalErb-b2 Receptor Tyrosine KinasesEstrogen Receptor alphaExonsFemaleGenotypeHumansLinkage DisequilibriumLymph NodesMembrane ProteinsMiddle Aged3' Untranslated RegionsErb-b2 Receptor Tyrosine KinasesEstrogen Receptor alphaKSR-1 protein kinaseLMTK3 protein, humanMembrane ProteinsProtein KinasesProtein Serine-Threonine KinasesTamoxifen

Identifiers

PMID25287073
OpenAlexW2033017336

What OpenQuestion holds

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Registered trials

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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.