Genomic Grade Index: An important tool for assessing breast cancer tumor grade and prognosis

Filho, Otto Metzger; Ignatiadis, M.; Sotiriou, Christos

doi:10.1016/j.critrevonc.2010.01.011

Cited by 57 publications

(21 citation statements)

References 48 publications

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“…This is in sharp contrast to ER- tumors, for which the recurrence rate peaks at around two years but diminishes to a low rate after five years (13). Current prognostic markers often focus on and are reasonably good at predicting early recurrences within five years (14-17), but the risk of late recurrences remains poorly predictable. Is late recurrence merely a reflection of very slowly proliferating ER+ cancer cells lying in distant sites or due to cancer cells actually entering a period of total dormancy in which they stop proliferating until they are activated to grow again by some as yet unknown stimulus.…”

Section: Clinical Manifestation Of Dormancy Of Er+ Breast Cancermentioning

confidence: 99%

Metastasis Dormancy in Estrogen Receptor–Positive Breast Cancer

Zhang

Giuliano

Trivedi³

et al. 2013

Clinical Cancer Research

213

181

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About 20-40% of breast cancer patients eventually develop recurrences in distant organs, which are often not detected until years to decades after the primary tumor diagnosis. This phenomenon is especially pronounced in ER+ breast cancer, suggesting that ER+ cancer cells may stay dormant for a protracted period of time, despite adjuvant therapies. Multiple mechanisms have been proposed to explain how cancer cells survive and remain in dormancy , and how they become reactivated and exit dormancy. These mechanisms include angiogenic switch, immunosurveillance, and interaction with extracellular matrix (ECM) and stromal cells. How to eradicate or suppress these dormant cancer cells remains a major clinical issue because of the lack of knowledge about the biological and clinical nature of these cells. Herein, we review the clinical manifestation of metastasis dormancy in ER+ tumors, the current biological insights of tumor dormancy obtained from various experimental models, and the clinical challenges to predict, detect, and treat dormant metastases. We also discuss future research directions toward a better understanding of the biological mechanisms and clinical management of ER+ dormant metastasis.

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Section: Clinical Manifestation Of Dormancy Of Er+ Breast Cancermentioning

confidence: 99%

Metastasis Dormancy in Estrogen Receptor–Positive Breast Cancer

Zhang

Giuliano

Trivedi³

et al. 2013

Clinical Cancer Research

213

181

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“…When only genome-wide microarray-based expression profiling was used, two different strategies were adopted to provide prognostic information by means of gene expression signatures [11]: following a “top-down” strategy, mRNA expression profiling from patients with known clinical outcome were statistically compared to identify signatures associated with different prognosis, without any biological assumption [12]; following a “bottom-up” strategy, mRNA expression profiling from patients with different tumor biological characteristics were selected and reduced in number following analysis through multivariate models [13]–[15], with a potential cost reduction of genomic biomarker analysis.…”

Section: Introductionmentioning

confidence: 99%

Integration of mRNA Expression Profile, Copy Number Alterations, and microRNA Expression Levels in Breast Cancer to Improve Grade Definition

et al. 2014

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Defining the aggressiveness and growth rate of a malignant cell population is a key step in the clinical approach to treating tumor disease. The correct grading of breast cancer (BC) is a fundamental part in determining the appropriate treatment. Biological variables can make it difficult to elucidate the mechanisms underlying BC development. To identify potential markers that can be used for BC classification, we analyzed mRNAs expression profiles, gene copy numbers, microRNAs expression and their association with tumor grade in BC microarray-derived datasets. From mRNA expression results, we found that grade 2 BC is most likely a mixture of grade 1 and grade 3 that have been misclassified, being described by the gene signature of either grade 1 or grade 3. We assessed the potential of the new approach of integrating mRNA expression profile, copy number alterations, and microRNA expression levels to select a limited number of genomic BC biomarkers. The combination of mRNA profile analysis and copy number data with microRNA expression levels led to the identification of two gene signatures of 42 and 4 altered genes (FOXM1, KPNA4, H2AFV and DDX19A) respectively, the latter obtained through a meta-analytical procedure. The 42-based gene signature identifies 4 classes of up- or down-regulated microRNAs (17 microRNAs) and of their 17 target mRNA, and the 4-based genes signature identified 4 microRNAs (Hsa-miR-320d, Hsa-miR-139-5p, Hsa-miR-567 and Hsa-let-7c). These results are discussed from a biological point of view with respect to pathological features of BC. Our identified mRNAs and microRNAs were validated as prognostic factors of BC disease progression, and could potentially facilitate the implementation of assays for laboratory validation, due to their reduced number.

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“…These are powerful prognosticators, but these may be only rough measures of the biological behavior of a tumor. Moreover, some of these parameters might be influenced by the subjectivity of the pathologist and limited in their prognostic value [11], [12]. Thus, it is valuable to find other prognostic markers, which can be measured reliably to support these traditional factors, and can then be used to help in evaluating patient’s risks and selection of treatment [13], [14].…”

Section: Introductionmentioning

confidence: 99%

Decreased Expression of C10orf10 and Its Prognostic Significance in Human Breast Cancer

Deng

Dong

et al. 2014

PLoS ONE

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Breast cancer is a common malignant tumor, which severely threatens the health of women with an increasing incidence in many countries. Here, we identified C10orf10 as a novel differentially expression gene using expression microarray screening. The expression analysis indicated that C10orf10 was frequently decreased in human breast cancers compared to noncancerous breast tissues (81/95, P = 0.0063). Kaplan-Meier analysis indicated that patients with low C10orf10 expression showed a poorer prognosis both in mRNA (n = 1115, P = 0.0013) and protein (n = 100, P = 0.003) levels. Univariate and multivariate analysis showed that the C10orf10 expression was an independent prognostic factor for overall survival of breast cancer patients. Further analysis revealed that low expression of C10orf10 was an unfavorable factor for the prognosis of the patients who were luminal A, luminal B, Her2+ subtypes, at histological grade 2, lymph node negative and ER positive. Our data provided the first evidence that C10orf10 expression was frequently decreased in breast cancer tissues, and low expression of C10orf10 may be an important prognostic factor for poorer survival time of breast cancer patients.

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Genomic Grade Index: An important tool for assessing breast cancer tumor grade and prognosis

Cited by 57 publications

References 48 publications

Metastasis Dormancy in Estrogen Receptor–Positive Breast Cancer

Metastasis Dormancy in Estrogen Receptor–Positive Breast Cancer

Integration of mRNA Expression Profile, Copy Number Alterations, and microRNA Expression Levels in Breast Cancer to Improve Grade Definition

Decreased Expression of C10orf10 and Its Prognostic Significance in Human Breast Cancer

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