Abstract:
INTRODUCTION:Gene expression analysis is used to subtype breast cancers such that the most aggressive tumors are identified, but translating this into clinical practice can be cumbersome. Our goal is to develop a universal biomarker that distinguishes patients at high risk across all breast cancer subtypes. We previously reported that Y-box binding protein-1 (YB-1), a transcription/translation factor, was a marker of poor prognosis in a cohort of 490 patients with breast cancer, but the study was not large enough to subtype the cancers. We therefore investigated whether YB-1 identifies patients at risk for either reduced relapse free survival or decreased r breast cancer specific survival (BCSS) across all tumor subtypes by evaluating 4,049 cases. METHODS:Tumor tissue microarrays, representing 4,049 cases of invasive breast cancers with 20 years of follow up, were subtyped by the expression profiles of estrogen receptor, progesterone receptor, or HER-2. We then addressed whether YB-1 expression identified patients at higher risk for relapse and/or lower BCSS. RESULTS:We found YB-1 to be a highly predictive biomarker of relapse (P < 2.5 x 10(-20)) and poor survival (P < 7.3 x 10(-26)) in the entire cohort and across all breast cancer subtypes. Patients with node-positive or node-negative cancer were more likely to die from the disease if YB-1 was expressed. This was further substantiated using a Cox regression model, which revealed that it was significantly associated with relapse and poor survival in a subtype independent manner (relapse patients, hazard ratio = 1.28, P < 8 x 10(-3); all patients, hazard ratio = 1.45, P < 6.7 x 10(-7)). Moreover, YB-1 was superior to estrogen receptor and HER-2 as a prognostic marker for relapse and survival. For a subset of patients who were originally considered low risk and were therefore not given chemotherapy, YB-1 was indicative of poor survival (P < 7.1 x 10 (-17)). Likewise, YB-1 was predictive of decreased BCSS in tamoxifen-treated patients (P = 0.001); in this setting a Cox regression model once again demonstrated it to be an independent biomarker indicating poor survival (hazard ratio = 1.70, P = 0.022). CONCLUSIONS:Expression of YB-1 universally identifies patients at high risk across all breast cancer subtypes and in situations where more aggressive treatment may be needed. We therefore propose that YB-1 may re-define high-risk breast cancer and thereby create opportunities for individualized therapy.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Habibi G,Leung S,Law JH,Gelmon K,Masoudi H,Turbin D,Pollak M,Nielsen TO,Huntsman D,Dunn SEdoi
10.1186/bcr2156subject
Has Abstractpub_date
2008-01-01 00:00:00pages
R86issue
5eissn
1465-5411issn
1465-542Xpii
bcr2156journal_volume
10pub_type
杂志文章abstract::It is hypothesized that the human homologue of the mouse mammary tumour virus (HHMMTV) and other viruses, such as human papillomavirus (HPV) and Epstein-Barr virus (EBV), act as cofactors with diet, oestrogens and other hormones in the initiation and promotion of some types of breast cancer in genetically susceptible ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr275
更新日期:2001-01-01 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: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::A small proportion of breast cancers are due to a heritable predisposition. Recently, two predisposition genes, BRCA1 and BRCA2, have been identified and cloned. The morphological features of tumours from patients harbouring mutations in the BRCA1 and BRCA2 genes differ from each other and from sporadic breast cancers...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr10
更新日期:1999-01-01 00:00:00
abstract:INTRODUCTION:Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be invo...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1617
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:Metastasis is a common event and the main cause of death in cancer patients. Lymphangiogenesis refers to the formation of new lymphatic vessels and is thought to be involved in the development of metastasis. Sunitinib is a multi-kinase inhibitor that blocks receptor tyrosine kinase activity, including that...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2903
更新日期:2011-06-21 00:00:00
abstract:BACKGROUND:The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast canc...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0953-7
更新日期:2018-04-16 00:00:00
abstract::Hypoxia-inducible factor-1 (HIF), which is centrally involved in physiological oxygen homeostasis, is also activated in the majority of tumours. Activation of HIF can occur through genetic mechanisms or as a result of hypoxia within the tumour microenvironment. In some cases HIF activation appears to be intimately lin...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr313
更新日期:2001-01-01 00:00:00
abstract::A series of recent studies have demonstrated that the retinoblastoma tumor suppressor (RB) pathway plays a critical role in multiple clinically relevant aspects of breast cancer biology, spanning early stage lesions to targeted treatment of metastatic disease. In ductal carcinoma in situ, multiple groups have shown th...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr3652
更新日期:2014-05-07 00:00:00
abstract::Progesterone receptor status is a marker for hormone responsiveness and disease prognosis in breast cancer. Progesterone receptor negative tumours have generally been shown to have a poorer prognosis than progesterone receptor positive tumours. The observed loss of progesterone receptor could be through a range of mec...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr2097
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:The aim of this study was to develop and validate a prognostication model to predict overall and breast cancer specific survival for women treated for early breast cancer in the UK. METHODS:Using the Eastern Cancer Registration and Information Centre (ECRIC) dataset, information was collated for 5,694 wom...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2464
更新日期:2010-01-01 00:00:00
abstract::For the past 20 years the mouse has served as a workhorse for studying the molecular underpinnings of human breast cancer. While some genetically engineered mouse mammary tumor models do not accurately recapitulate human disease (that is, the MMTV-Neu model and HER2-overexpressing human cancers), additional tumor mode...
journal_title:Breast cancer research : BCR
pub_type: 评论,社论
doi:10.1186/bcr2569
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Mammary stem cells are bipotential and suggested to be the origin of breast cancer development, but are elusive and vaguely characterized. Breast tumors can be divided into subgroups, each one requiring specific treatment. To determine a possible association between mammary stem cells and breast cancer, a ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2256
更新日期:2009-01-01 00:00:00
abstract::A new gene associated with a high risk of breast cancer, termed BRCAX, may exist on chromosome 13q. Tumours from multicase Nordic breast cancer families, in which mutations in BRCA1 and BRCA2 had been excluded, were analyzed using comparative genomic hybridization in order to identify a region of interest, which was a...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr290
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:The global observational BREAKOUT study investigated germline BRCA mutation (gBRCAm) prevalence in a population of patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). METHODS:Eligible patients had initiated first-line cytotoxic chemotherapy for HER2-negativ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/s13058-020-01349-9
更新日期:2020-10-27 00:00:00
abstract:PURPOSE:The therascreen PIK3CA mutation assay and the alpha-specific PI3K inhibitor alpelisib are FDA-approved for identifying and treating patients with advanced PIK3CA-mutated (PIK3CAmut) breast cancer (BC). However, it is currently unknown to what extend this assay detects most PIK3CA mutations in BC. This informati...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01284-9
更新日期:2020-05-13 00:00:00
abstract:INTRODUCTION:The status of tumor-infiltrating lymphocytes (TILs) has been recently proposed to predict clinical outcome of patients with breast cancer. We therefore studied the prognostic significance of CD8(+) TILs and FOXP3(+) TILs in residual tumors after neoadjuvant chemotherapy (NAC) and the alterations in these p...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/s13058-015-0632-x
更新日期:2015-09-04 00:00:00
abstract::As the release of tumor-associated DNA into blood circulation is a common event in patients with cancer, screening of plasma or serum DNA may provide information on genetic and epigenetic profiles associated with breast cancer development, progression, and response to therapy. Quantitative testing of circulating DNA c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/s13058-015-0645-5
更新日期:2015-10-09 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:INTRODUCTION:Human epidermal growth factor receptor HER3 has been implicated in promoting the aggressiveness and metastatic potential of breast cancer. Upregulation of HER3 has been found to be a major mechanism underlying drug resistance to EGFR and HER2 tyrosine kinase inhibitors and to endocrine therapy in the treat...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0528-9
更新日期:2015-02-15 00:00:00
abstract:BACKGROUND:The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear. METHODS:We have c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr419
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:Although recent models suggest that the detection of Circulating Tumor Cells (CTC) in epithelial-to-mesenchymal transition (EM CTC) might be related to disease progression in metastatic breast cancer (MBC) patients, current detection methods are not efficient in identifying this subpopulation of cells. Furth...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-016-0687-3
更新日期:2016-03-09 00:00:00
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::PIK3CA mutations represent one of the most common genetic aberrations in breast cancer. They have been reported to be present in over one-third of cases, with enrichment in the luminal and in human epidermal growth factor receptor 2-positive subtypes. Substantial preclinical data on the oncogenic properties of these m...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr3605
更新日期:2014-01-23 00:00:00
abstract:INTRODUCTION:Estrogen receptor-alpha (ER-alpha) and progesterone receptor (PgR) are consolidated predictors of response to hormonal therapy (HT). In contrast, little information regarding the role of estrogen receptor-beta (ER-beta) in various breast cancer risk groups treated with different therapeutic regimens is ava...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2139
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:In breast cancer, BRCA promoter hypermethylation and BRCA germline mutations are said to occur together rarely, but this property has not yet been translated into a clinical test. Our aim in this study was to investigate the diagnostic value of BRCA1/2 methylation in distinguishing breast carcinomas of BRCA1...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0856-z
更新日期:2017-05-31 00:00:00
abstract:INTRODUCTION:There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. METHODS:We...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3625
更新日期:2014-03-14 00:00:00
abstract:INTRODUCTION:Focal adhesion kinase (FAK) regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis. In breast carcinoma, FAK overexpression has been linked to cancer progression but the prognostic relevance remains unknown. In particular, with regard to lymph node-negativ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr977
更新日期:2005-01-01 00:00:00
abstract::The Breast Cancer Site Group (BCSG) of the National Cancer Institute of Canada (NCIC) Clinical Trials Group (CTG) has conducted a wide variety of clinical trials focussing on large phase III trials of adjuvant chemotherapy, adjuvant hormonal therapy, and optimal delivery of adjuvant radiation therapy. The Group has al...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr979
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Current approaches to inhibit oestrogen receptor-alpha (ERα) are focused on targeting its hormone-binding pocket and have limitations. Thus, we propose that inhibitors that bind to a coactivator-binding pocket on ERα, called activation function 2 (AF2), might overcome some of these limitations. METHODS:In...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0529-8
更新日期:2015-02-25 00:00:00