Abstract:
INTRODUCTION:The potential of applying data analysis tools to microarray data for diagnosis and prognosis is illustrated on the recent breast cancer dataset of van 't Veer and coworkers. We re-examine that dataset using the novel technique of logical analysis of data (LAD), with the double objective of discovering patterns characteristic for cases with good or poor outcome, using them for accurate and justifiable predictions; and deriving novel information about the role of genes, the existence of special classes of cases, and other factors. METHOD:Data were analyzed using the combinatorics and optimization-based method of LAD, recently shown to provide highly accurate diagnostic and prognostic systems in cardiology, cancer proteomics, hematology, pulmonology, and other disciplines. RESULTS:LAD identified a subset of 17 of the 25,000 genes, capable of fully distinguishing between patients with poor, respectively good prognoses. An extensive list of 'patterns' or 'combinatorial biomarkers' (that is, combinations of genes and limitations on their expression levels) was generated, and 40 patterns were used to create a prognostic system, shown to have 100% and 92.9% weighted accuracy on the training and test sets, respectively. The prognostic system uses fewer genes than other methods, and has similar or better accuracy than those reported in other studies. Out of the 17 genes identified by LAD, three (respectively, five) were shown to play a significant role in determining poor (respectively, good) prognosis. Two new classes of patients (described by similar sets of covering patterns, gene expression ranges, and clinical features) were discovered. As a by-product of the study, it is shown that the training and the test sets of van 't Veer have differing characteristics. CONCLUSION:The study shows that LAD provides an accurate and fully explanatory prognostic system for breast cancer using genomic data (that is, a system that, in addition to predicting good or poor prognosis, provides an individualized explanation of the reasons for that prognosis for each patient). Moreover, the LAD model provides valuable insights into the roles of individual and combinatorial biomarkers, allows the discovery of new classes of patients, and generates a vast library of biomedical research hypotheses.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Alexe G,Alexe S,Axelrod DE,Bonates TO,Lozina II,Reiss M,Hammer PLdoi
10.1186/bcr1512subject
Has Abstractpub_date
2006-01-01 00:00:00pages
R41issue
4eissn
1465-5411issn
1465-542Xpii
bcr1512journal_volume
8pub_type
杂志文章abstract:INTRODUCTION:Mammographic density has been established as a strong risk factor for breast cancer, primarily using digitized film mammograms. Full-field digital mammography (FFDM) is replacing film mammography, has different properties than film, and provides both raw and processed clinical display representation images...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3372
更新日期:2013-01-04 00:00:00
abstract:INTRODUCTION:Hypoxia-inducible factor (HIF)-1alpha levels in invasive breast carcinoma have been shown to be an adverse prognostic indicator. Cellular HIF-1alpha activity is regulated by factor-inhibiting hypoxia-inducible factor 1 (FIH-1). In hypoxia, FIH-1 hydroxylation of Asn803 within the C-terminal transactivation...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1838
更新日期:2007-01-01 00:00:00
abstract::The concept of 'targeted' therapies implies that such drugs only act on cells that specifically express the particular target, therefore giving rise to a low incidence of side effects. However, targeted therapies currently approved for the treatment of breast cancer have demonstrated a relatively high incidence of car...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr3142
更新日期:2012-06-19 00:00:00
abstract::The key to optimising our approach in early breast cancer is to individualise care. Each patient has a tumour with innate features that dictate their chance of relapse and their responsiveness to treatment. Often patients with similar clinical and pathological tumours will have markedly different outcomes and response...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr2238
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Mammary-specific overexpression of Six1 in mice induces tumors that resemble human breast cancer, some having undergone epithelial to mesenchymal transition (EMT) and exhibiting stem/progenitor cell features. Six1 overexpression in human breast cancer cells promotes EMT and metastatic dissemination. We hyp...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3219
更新日期:2012-07-05 00:00:00
abstract:INTRODUCTION:17-allyamino-17-demethoxygeldanamycin (17-AAG), a small molecule inhibitor of Hsp90, is currently in clinical trials in breast cancer. However, 17-AAG treatment often results in inhibition of tumor growth rather than shrinkage, making detection of response a challenge. Magnetic resonance spectroscopy (MRS)...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2729
更新日期:2010-01-01 00:00:00
abstract::Certain laminins of vascular basement membranes have been identified in human breast tumors and brain gliomas that share the same beta1 chain. These laminins are new carcinoma angiogenic markers and might represent potential targets for antiangiogenic therapy. ...
journal_title:Breast cancer research : BCR
pub_type: 评论,杂志文章
doi:10.1186/bcr1270
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Breast tumor kinase (Brk/protein tyrosine kinase 6 (PTK6)) is a nonreceptor, soluble tyrosine kinase overexpressed in the majority of breast tumors. Previous work has placed Brk downstream of epidermal growth factor receptor (ErbB) activation and upstream of extracellular signal-regulated kinase 5 (ERK5) a...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2622
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Recent genome-wide profiling by sequencing and distinctive chromatin signatures has identified thousands of long non-coding RNA (lncRNA) species (>200 nt). LncRNAs have emerged as important regulators of gene expression, involving in both developmental and pathological processes. While altered expression of ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0853-2
更新日期:2017-05-30 00:00:00
abstract:BACKGROUND:Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. METHODS:We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations w...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0954-6
更新日期:2018-04-17 00:00:00
abstract:BACKGROUND:Tumor hypoxia is an independent prognostic factor associated with poor patient survival. Emerging evidence suggests that hypoxia can potentially maintain or enhance the stem cell phenotype of both normal stem cells and cancer cells. However, it remains to be determined whether cell fate is regulated in vivo ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0944-8
更新日期:2018-03-06 00:00:00
abstract:BACKGROUND:African American/Black women with breast cancer have poorer survival than White women, and this disparity persists even after adjusting for non-biological factors. Differences in tumor immune biology have been reported between Black and White women, and the tumor immune milieu could potentially drive racial ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/s13058-020-01297-4
更新日期:2020-06-09 00:00:00
abstract:INTRODUCTION:Matrix metalloproteinase (MMP)-2 is very active at degrading extracellular matrix. It is under the influence of an activator, membrane type 1 MMP (MMP-14), and the tissue inhibitor of metalloproteases (TIMP)-2. We hypothesized that the individual expression of these three markers or their balance may help ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1503
更新日期:2006-01-01 00:00:00
abstract::Following publication of the original article [1], the authors reported a typesetting error in the spelling of the second author's name. ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13058-018-1069-9
更新日期:2018-11-19 00:00:00
abstract::Targeting the function of epidermal growth factor receptor (EGFR) has failed as an effective clinical option for breast cancer. Understanding the drivers of inherent resistance has been a challenge. One possible mechanism is the acquisition of stem-like properties through the process of epithelial-mesenchymal transiti...
journal_title:Breast cancer research : BCR
pub_type: 评论,杂志文章
doi:10.1186/s13058-014-0448-0
更新日期:2014-09-23 00:00:00
abstract:INTRODUCTION:Aberrant activation of Wnt/β-catenin signaling plays an important role in the pathogenesis of breast cancer. DACT1 (Dapper/Frodo) has been identified as involved in antagonizing Wnt/β-catenin signaling through interacting with Dishevelled (Dvl), a central mediator of Wnt signaling, whereas its role in brea...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3399
更新日期:2013-03-12 00:00:00
abstract:BACKGROUND:The tamoxifen metabolite, Z-endoxifen, demonstrated promising antitumor activity in endocrine-resistant estrogen receptor-positive (ER+) breast cancer. We compared the antitumor activity of Z-endoxifen with tamoxifen and letrozole in the letrozole-sensitive MCF7 aromatase expressing model (MCF7AC1), as well ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01286-7
更新日期:2020-05-19 00:00:00
abstract::A recent analysis by the Collaborative Group on Hormonal Factors in Breast Cancer has provided the most precise quantification to date of the familial risks of breast cancer. The familial relative risks are shown to decrease from more than fivefold in women younger than age 40 years with a first-degree relative aged y...
journal_title:Breast cancer research : BCR
pub_type: 社论
doi:10.1186/bcr448
更新日期:2002-01-01 00:00:00
abstract::STATEMENT OF FINDINGS: We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor char...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr82
更新日期:2000-01-01 00:00:00
abstract::Despite the progress achieved in breast cancer screening and therapeutic innovations, the basal-like subtype of breast cancer (BLBC) still represents a particular clinical challenge. In order to make an impact on survival in this type of aggressive breast cancer, new targeted therapeutic agents are urgently needed. Ab...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr3401
更新日期:2013-03-28 00:00:00
abstract:INTRODUCTION:The main prognostic variables in early breast cancer are tumor size, histological grade, estrogen receptor/progesterone receptor (ER/PgR) status, number of positive nodes and human epidermal growth factor receptor 2 (HER2) status. The present study evaluated the prognostic and/or predictive value of vascul...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,随机对照试验
doi:10.1186/bcr3354
更新日期:2012-11-12 00:00:00
abstract::Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr26
更新日期:2000-01-01 00:00:00
abstract:INTRODUCTION:BRCA1 and BRCA2 mutation carriers are at increased risk for developing both breast and ovarian cancer. It has been suggested that carriers of BRCA1/2 mutations may also be at increased risk of having recurrent (three or more) miscarriages. Several reproductive factors have been shown to influence the risk ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/bcr1387
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:We previously performed a case-control genome-wide association study in women treated with selective estrogen receptor modulators (SERMs) for breast cancer prevention and identified single nucleotide polymorphisms (SNPs) in ZNF423 as potential biomarkers for response to SERM therapy. The ZNF423rs9940645 SNP,...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0890-x
更新日期:2017-08-18 00:00:00
abstract:BACKGROUND:The relationship between breast cancer and thyroid diseases is controversial. Discrepant results have been reported in the literature. The incidences of autoimmune and nonautoimmune thyroid diseases were investigated in patients with breast cancer and age-matched control individuals without breast or thyroid...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr609
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Breast magnetic resonance imaging (MRI) has been reported to frequently result in false-positive diagnoses, limiting its positive predictive value (PPV). However, for PPV calculation, all nonmalignant tissue changes are equally considered false-positive, although the respective prognostic importance, and thu...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0937-7
更新日期:2018-02-09 00:00:00
abstract::Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of inducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr297
更新日期:2001-01-01 00:00:00
abstract:INTRODUCTION:Metastasis of breast cancer is the main cause of death in patients. Previous genome-wide studies have identified gene-expression patterns correlated with cancer patient outcome. However, these were derived mostly from whole tissue without respect to cell heterogeneity. In reality, only a small subpopulatio...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3344
更新日期:2012-10-31 00:00:00
abstract:INTRODUCTION:Triple-negative breast cancer (TNBC), a subtype of breast cancer with negative expressions of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), is frequently diagnosed in younger women and has poor prognosis for disease-free and overall survival. Due to the lack...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3575
更新日期:2013-11-12 00:00:00
abstract:INTRODUCTION:The actin binding protein Mammalian enabled (Mena), has been implicated in the metastatic progression of solid tumors in humans. Mena expression level in primary tumors is correlated with metastasis in breast, cervical, colorectal and pancreatic cancers. Cells expressing high Mena levels are part of the tu...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2784
更新日期:2010-01-01 00:00:00