Evidence mapPaperPMID 25421723Full record

ArticleCarcinogenesis2015

Comparison of tamoxifen and letrozole response in mammary preneoplasia of ER and aromatase overexpressing mice defines an immune-associated gene signature linked to tamoxifen resistance.

Sarah A Dabydeen, Keunsoo Kang, Edgar S Díaz-Cruz, Ahmad Alamri, Margaret L Axelrod, Kerrie B Bouker, Rawan Al-Kharboosh, Robert Clarke, Lothar Hennighausen, Priscilla A Furth

Open access · greenAbstract readComparative Study
In one paragraph

Article in Carcinogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. The immunomodulatory effects of endocrine therapy in breast cancer.Journal of experimental & clinical cancer research : CR · 2021
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Responsiveness ofCancer prevention research (Philadelphia, Pa.) · 2017
    Article
  12. Article
  13. Article
  14. 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

10 authors at 4 institutions in 3 countries.

Sarah A DabydeenDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Keunsoo KangLaboratory Genetics and Physiology, NIDDK, NIH, Bethesda, MD 20892, USA Department of Microbiology, Dankook University, Cheonan 330-714, Republic of Korea.
Edgar S Díaz-CruzDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA, Department of Pharmaceutical, Social, & Administrative Sciences, Belmont University College of Pharmacy, Nashville, TN 37212, USA.
Ahmad AlamriDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA, Clinical Laboratories Sciences, College of Applied Medical Sciences, King Khalid University, Abha 62529, Saudi Arabia and.
Margaret L AxelrodDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Kerrie B BoukerDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Rawan Al-KharbooshDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Robert ClarkeDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Lothar HennighausenLaboratory Genetics and Physiology, NIDDK, NIH, Bethesda, MD 20892, USA.
Priscilla A FurthDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA, Department of Medicine, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA paf3@georgetown.edu.
Georgetown University Medical Center · USGeorgetown University · USNational Institutes of Health · USKing Khalid University · SA

Funding

Tissue Culture and Biobanking Shared ResourceP30CA051008 · GEORGETOWN UNIVERSITY · 1990 to 2025
$20.3M
Genetic Approaches To Understanding Organ Development and FunctionZIADK061000 · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2025 to 2025
$2.9M
TRAINING GRANT IN TUMOR BIOLOGYT32CA009686 · GEORGETOWN UNIVERSITY · 1996 to 2025
$2.2M
Progression and regression of mammary preneoplasiaR01CA112176 · GEORGETOWN UNIVERSITY · 2005 to 2005
$286k
Intramural NIH HHSNCI NIH HHS 5T32CA009686-15NCI NIH HHS BC130883NCI NIH HHS CA112176NCI NIH HHS NCI U54CA149147NCI NIH HHS NIH NCI 5P30CA051008NCRR NIH HHS NIH IG20RR025828
6 · The paper itself

Abstract

Response to breast cancer chemoprevention can depend upon host genetic makeup and initiating events leading up to preneoplasia. Increased expression of aromatase and estrogen receptor (ER) is found in conjunction with breast cancer. To investigate response or resistance to endocrine therapy, mice with targeted overexpression of Esr1 or CYP19A1 to mammary epithelial cells were employed, representing two direct pathophysiological interventions in estrogen pathway signaling. Both Esr1 and CYP19A1 overexpressing mice responded to letrozole with reduced hyperplastic alveolar nodule prevalence and decreased mammary epithelial cell proliferation. CYP19A1 overexpressing mice were tamoxifen sensitive but Esr1 overexpressing mice were tamoxifen resistant. Increased ER expression occurred with tamoxifen resistance but no consistent changes in progesterone receptor, pSTAT3, pSTAT5, cyclin D1 or cyclin E levels in association with response or resistance were found. RNA-sequencing (RNA-seq) was employed to seek a transcriptome predictive of tamoxifen resistance using these models and a second tamoxifen-resistant model, BRCA1 deficient/Trp53 haploinsufficient mice. Sixty-eight genes associated with immune system processing were upregulated in tamoxifen-resistant Esr1- and Brca1-deficient mice, whereas genes related to aromatic compound metabolic process were upregulated in tamoxifen-sensitive CYP19A1 mice. Interferon regulatory factor 7 was identified as a key transcription factor regulating these 68 immune processing genes. Two loci encoding novel transcripts with high homology to human immunoglobulin lambda-like polypeptide 1 were uniquely upregulated in the tamoxifen-resistant models. Letrozole proved to be a successful alternative to tamoxifen. Further study of transcriptional changes associated with tamoxifen resistance including immune-related genes could expand our mechanistic understanding and lead to biomarkers predictive of escape or response to endocrine therapies.

Indexed as

AnimalsAntineoplastic Agents, HormonalAromataseAromatase InhibitorsBiomarkers, TumorBRCA1 ProteinDrug Resistance, NeoplasmEstrogen Receptor alphaFemaleFlow CytometryGene Expression ProfilingGene Regulatory NetworksHumansImmune System PhenomenaImmunoenzyme TechniquesLetrozoleAntineoplastic Agents, HormonalAromataseAromatase InhibitorsBiomarkers, TumorBRCA1 ProteinEstrogen Receptor alphaLetrozoleNitrilesRNA, MessengerTamoxifenTriazoles

Identifiers

PMID25421723
PMCPMC4291054
OpenAlexW2124558272

What Socratic holds

Textmetadata
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 Socratic graph.