Overexpression of Eukaryotic Initiation Factor 4E Is Correlated with Increased Risk for Systemic Dissemination in Node-Positive Breast Cancer Patients

Yin, Xuedong; Kim, Roger H.; Sun, Guang; Miller, J. Karen; Li, Benjamin D.

doi:10.1016/j.jamcollsurg.2013.12.020

Cited by 13 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, eIF4E and its associated binding proteins have been shown to correlate with survival duration in FBC, where cases with high expression of eIF4E relative to its binding proteins had significantly worse survival (20). Our results corroborate these and other findings where elevated eIF4E expression predicts poor survival in FBC (21,29,30).…”

Section: Discussionsupporting

confidence: 89%

“…>70% as well as concordance with previous literature (20,21,29,30) are significant strengths, all pointing toward eIF4E being a poor prognostic factor in breast cancer, irrespective of gender. Given that we wished to identify potential gender-specific differences in gene expression in breast cancer, this result may be perceived as surprising.…”

Section: Discussionsupporting

confidence: 88%

See 1 more Smart Citation

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Humphries

Rajan

Droop

et al. 2017

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n ¼ 477, training; n ¼ 220, validation set) and quantified in pre-and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P ¼ 0.013; HR ¼ 1.77, 1.12-2.8 and P ¼ 0.035; HR ¼ 1.68, 1.03-2.74, respectively), or when coexpressed (P ¼ 0.01; HR ¼ 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P ¼ 0.016; HR ¼ 2.38 (1.18-4.8), eIF5 P ¼ 0.022; HR ¼ 2.55 (1.14-5.7); coexpression P ¼ 0.001; HR ¼ 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival.Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 88%

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Humphries

Rajan

Droop

et al. 2017

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Ki-67, a marker for proliferating cells and overexpression in many breast cancers, is a time-varying biomarker of breast cancer in women with atypical hyperplasia 50. High expression of eukaryotic initiation factor 4E is associated with an increased risk for systemic metastasis in node-positive breast cancer patients 51. SEER dataset is used to classify patient survival, status and cancer stage between tumor tissue, positive or negative.…”

Section: Surveillance Epidemiology and End Resultsmentioning

confidence: 99%

Identification of Biomarkers for Breast Cancer Using Databases

Lee

Moon

2016

J Cancer Prev

View full text Add to dashboard Cite

Breast cancer is one of the major causes of cancer death in women. Many studies have sought to identify specific molecules involved in breast cancer and understand their characteristics. Many biomarkers which are easily measurable, dependable, and inexpensive, with a high sensitivity and specificity have been identified. The rapidly increasing technology development and availability of epigenetic informations play critical roles in cancer. The accumulated data have been collected, stored, and analyzed in various types of databases. It is important to acknowledge useful and available data and retrieve them from databases. Nowadays, many researches utilize the databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Surveillance, Epidemiology and End Results (SEER), and Embase, to find useful informations on biomarkers for breast cancer. This review summarizes the current databases which have been utilized for identification of biomarkers for breast cancer. The information provided by this review would be beneficial to seeking appropriate strategies for diagnosis and treatment of breast cancer.

show abstract

“…A second study a few years later found similar results 118. Among patients undergoing primary debulking for a node-positive breast cancer when nodes were positive, after 4-year followup, systemic recurrence occurred in 22% of women with low eIF4E protein expression, 27% of the intermediate group, and in 49% expressing large amounts of eIF4E 119. Even more serious was the presence of multiple distant metastases in 60% of women whose primary expressed large amounts of eIF4E but in 15% of women whose primary expressed low amounts of eIF4E, again after 4-year follow-up 119…”

Section: Drugs To Inhibit Emtmentioning

confidence: 75%

The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy

Kast¹,

Skuli

Cos

et al. 2017

BCTT

View full text Add to dashboard Cite

Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities. Chemotherapy, radiation, and surgery provoke EMT in cancer generally and in breast cancer specifically. ABC7 uses standard doses of capecitabine as used in treating breast cancer today. In addition, ABC7 uses 1) an older psychiatric drug, quetiapine, to block RANK signaling; 2) pirfenidone, an anti-fibrosis drug to block TGF-beta signaling; 3) rifabutin, an antibiotic to block beta-catenin signaling; 4) metformin, a first-line antidiabetic drug to stimulate AMPK and inhibit mammalian target of rapamycin, (mTOR); 5) propranolol, a beta-blocker to block beta-adrenergic signaling; 6) agomelatine, a melatonergic antidepressant to stimulate M1 and M2 melatonergic receptors; and 7) ribavirin, an antiviral drug to prevent eIF4E phosphorylation. All these block the signaling pathways – RANK, TGF-beta, mTOR, beta-adrenergic receptors, and phosphorylated eIF4E – that have been shown to trigger EMT and enhance breast cancer growth and so are worthwhile targets to inhibit. Agonism at MT1 and MT2 melatonergic receptors has been shown to inhibit both breast cancer EMT and growth. This ensemble was designed to be safe and augment capecitabine efficacy. Given the expected outcome of metastatic breast cancer as it stands today, ABC7 warrants a cautious trial.

show abstract

Overexpression of Eukaryotic Initiation Factor 4E Is Correlated with Increased Risk for Systemic Dissemination in Node-Positive Breast Cancer Patients

Cited by 13 publications

References 35 publications

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Identification of Biomarkers for Breast Cancer Using Databases

The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy

Contact Info

Product

Resources

About