Evidence map›Paper›PMID 26285647›Full record

ArticleMolecular oncology2016

4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer.

Tommaso De Marchi, Ning Qing Liu, Cristoph Stingl, Mieke A Timmermans, Marcel Smid, Maxime P Look, Mila Tjoa, Rene B H Braakman, Mark Opdam, Sabine C Linn and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

23 citing papers in PubMed, 40 citations in OpenAlex.

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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 5 institutions in 1 country.

Tommaso De MarchiDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands; Postgraduate School of Molecular Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: t.demarchi@erasmusmc.nl.
Ning Qing LiuDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: n.liu@ncmls.ru.nl.
Cristoph StinglDepartment of Neurology, Erasmus MC, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: c.stingl@erasmusmc.nl.
Mieke A TimmermansDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: a.timmermans@erasmusmc.nl.
Marcel SmidDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: m.smid@erasmusmc.nl.
Maxime P LookDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: m.look@erasmusmc.nl.
Mila TjoaDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: milatjoa@hotmail.com.
Rene B H BraakmanDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands; Postgraduate School of Molecular Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: r.braakman@erasmusmc.nl.
Mark OpdamDivision of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. Electronic address: m.opdam@nki.nl.
Sabine C LinnDivision of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. Electronic address: s.linn@nki.nl.
Fred C G J SweepDepartment of Laboratory Medicine, Radboud University Medical Center, PO Box 9101, NL-6500 HB, Nijmegen, The Netherlands. Electronic address: f.sweep@labgk.umcn.nl.
Paul N SpanDepartment of Radiation Oncology, Radboud University Medical Center, PO Box 9101, NL-6500 HB, Nijmegen, The Netherlands. Electronic address: P.Span@rther.umcn.nl.
Mike KliffenDepartment of Pathology, Maasstad Hospital, Maasstadweg 21, 3079 DZ, Rotterdam, The Netherlands. Electronic address: KliffenM@maasstadziekenhuis.nl.
Theo M LuiderDepartment of Neurology, Erasmus MC, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: t.luider@erasmusmc.nl.
John A FoekensDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: j.foekens@erasmsumc.nl.
John W M MartensDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands; Cancer Genomics Center Netherlands, Amsterdam, The Netherlands. Electronic address: j.martens@erasmusmc.nl.
Arzu UmarDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: a.umar@erasmsumc.nl.
Erasmus MC Cancer Institute · NLErasmus MC · NLRadboud University Medical Center · NLThe Netherlands Cancer Institute · NLMaasstad Ziekenhuis · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity in complex tumor tissue was reduced using laser capture microdissection (LCM). In the current study, we performed high resolution proteomic analysis on two cohorts of ER positive breast tumors derived from patients who either manifested good or poor outcome to tamoxifen treatment upon recurrence. A total of 112 fresh frozen tumors were collected from multiple medical centers and divided into two sets: an in-house training and a multi-center test set. Epithelial tumor cells were enriched with LCM and analyzed by nano-LC Orbitrap mass spectrometry (MS), which yielded >3000 and >4000 quantified proteins in the training and test sets, respectively. Raw data are available via ProteomeXchange with identifiers PXD000484 and PXD000485. Statistical analysis showed differential abundance of 99 proteins, of which a subset of 4 proteins was selected through a multivariate step-down to develop a predictor for tamoxifen treatment outcome. The 4-protein signature significantly predicted poor outcome patients in the test set, independent of predictive histopathological characteristics (hazard ratio [HR] = 2.17; 95% confidence interval [CI] = 1.15 to 4.17; multivariate Cox regression p value = 0.017). Immunohistochemical (IHC) staining of PDCD4, one of the signature proteins, on an independent set of formalin-fixed paraffin-embedded tumor tissues provided and independent technical validation (HR = 0.72; 95% CI = 0.57 to 0.92; multivariate Cox regression p value = 0.009). We hereby report the first validated protein predictor for tamoxifen treatment outcome in recurrent ER-positive breast cancer. IHC further showed that PDCD4 is an independent marker.

Indexed as

Antineoplastic Agents, HormonalBreast NeoplasmsFemaleHumansMiddle AgedNeoplasm ProteinsNeoplasm Recurrence, LocalTamoxifenTreatment OutcomeAntineoplastic Agents, HormonalNeoplasm ProteinsTamoxifenBiomarkerBreast cancerMass spectrometryProteomicsTamoxifen resistance

Identifiers

PMID26285647
PMCPMC5528925
OpenAlexW1219777200

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.