Abstract:
INTRODUCTION:Primary breast cancer involving four or more axillary lymph nodes carries a poor prognosis. We hypothesized that use of an immunohistochemical biomarker scoring system could allow for identification of variable risk subgroups. METHODS:Patients with four or more positive axillary nodes were identified from a clinically annotated tissue microarray of formalin-fixed paraffin-embedded primary breast cancers and randomized into a 'test set' and a 'validation set'. A prospectively defined prognostic scoring model was developed in the test set and was further assessed in the validation set combining expression for eight biomarkers by immunohistochemistry, including estrogen receptor, human epidermal growth factor receptors 1 and 2, carbonic anhydrase IX, cytokeratin 5/6, progesterone receptor, p53 and Ki-67. Survival outcomes were analyzed by the Kaplan-Meier method, log rank tests and Cox proportional-hazards models. RESULTS:A total of 313 eligible patients were identified in the test set for whom 10-year relapse-free survival was 38.3% (SEM 2.9%), with complete immunohistochemical data available for 227. Tumor size, percentage of positive axillary nodes and expression status for the progesterone receptor, Ki-67 and carbonic anhydrase IX demonstrated independent prognostic significance with respect to relapse-free survival. Our combined biomarker scoring system defined three subgroups in the test set with mean 10-year relapse-free survivals of 75.4% (SEM 7.0%), 35.3% (SEM 4.1%) and 19.3% (SEM 7.0%). In the validation set, differences in relapse-free survival for these subgroups remained statistically significant but less marked. CONCLUSION:Biomarkers assessed here carry independent prognostic value for breast cancer with four or more positive axillary nodes and identified clinically relevant prognostic subgroups. This approach requires refinement and validation of methodology.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Crabb SJ,Bajdik CD,Leung S,Speers CH,Kennecke H,Huntsman DG,Gelmon KAdoi
10.1186/bcr1847subject
Has Abstractpub_date
2008-01-01 00:00:00pages
R6issue
1eissn
1465-5411issn
1465-542Xpii
bcr1847journal_volume
10pub_type
杂志文章,随机对照试验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:INTRODUCTION:Aromatase inhibitor-associated arthralgia (AIAA) is a common and often debilitating symptom in breast cancer survivors. Since joint symptoms have been related to estrogen deprivation through the menopausal transition, we hypothesized that genetic polymorphisms in CYP19A1, the final enzyme in estrogen synth...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2813
更新日期:2011-01-20 00:00:00
abstract:INTRODUCTION:Compromised patterns of gene expression result in genomic instability, altered patterns of gene expression and tumour formation. Specifically, aberrant DNA hypermethylation in gene promoter regions leads to gene silencing, whereas global hypomethylation events can result in chromosomal instability and onco...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr799
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Human epidermal growth factor receptor-2 (HER2) gene amplification (HER2+) drives tumor cell growth and survival in ~25% of breast cancers. HER2 signaling activates the type I phosphoinositide 3-kinase (PI3K), upon which these tumors rely. Consequently, inhibitors of HER2 and type I PI3K block growth and i...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0656-2
更新日期:2015-12-04 00:00:00
abstract:BACKGROUND:Vitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highe...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1169-1
更新日期:2019-07-29 00:00:00
abstract:BACKGROUND:Black-white disparities in breast cancer incidence rates and birth outcomes raise concerns about potential disparities in the reproductive health of premenopausal breast cancer survivors. We examined the prevalence of preterm birth (PTB), low birthweight (LBW), and small for gestational age (SGA) by breast c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0803-z
更新日期:2017-01-31 00:00:00
abstract::Therapeutic choices for metastatic tumors are, in most cases, based upon the histological and molecular analysis of the corresponding primary tumor. Understanding whether and to what extent the genomic landscape of metastasis differs from the tumors from which they originated is critical yet largely unknown. A recent ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2469
更新日期:2010-01-01 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:INTRODUCTION:Increased mammographic breast density is one of the strongest risk factors for breast cancer. While two-thirds of the variation in mammographic density appears to be genetically influenced, few variants have been identified. We examined the association of inherited variation in genes from pathways that med...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3088
更新日期:2012-01-07 00:00:00
abstract::Transforming growth factor-beta (TGF-beta) is a tumor suppressor, the function of which is compromised in many types of human cancer, including breast cancer. The tumor suppressive effects of TGF-beta are caused by potent inhibition of cell proliferation due to cell cycle arrest in the G1 phase. Such antiproliferative...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr42
更新日期:2000-01-01 00:00:00
abstract:INTRODUCTION:We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined. METHODS:HMG-CoAR protein and RNA expr...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2820
更新日期:2011-01-31 00:00:00
abstract:INTRODUCTION:The majority of breast cancers that occur in BRCA1 mutation carriers (BRCA1 carriers) are estrogen receptor-negative (ER-). Therefore, it has been suggested that ER negativity is intrinsic to BRCA1 cancers and reflects the cell of origin of these tumors. However, approximately 20% of breast cancers that de...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2776
更新日期:2010-01-01 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:BACKGROUND:Breast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedb...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01262-1
更新日期:2020-03-13 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::The past decade has seen the definition of key signalling pathways downstream of receptor tyrosine kinases (RTKs) in terms of their components and the protein-protein interactions that facilitate signal transduction. Given the strong evidence that links signalling by certain families of RTKs to the progression of brea...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr54
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Bone is one of the most frequent metastatic sites of advanced breast cancer. Current therapeutic agents aim to inhibit osteoclast-mediated bone resorption but only have palliative effects. During normal bone remodeling, the balance between bone resorption and osteoblast-mediated bone formation is essential f...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-1059-y
更新日期:2018-10-22 00:00:00
abstract::Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell cycle and immunohistochemistry of proliferation-associated antigens. The evidence, advantages and disadvantages for each of these methods along with ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr1618
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:Breast tumors are comprised of distinct cancer cell populations which differ in their tumorigenic and metastatic capacity. Characterization of cell surface markers enables investigators to distinguish between cancer stem cells and their counterparts. CD24 is a well-known cell surface marker for mammary epi...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0589-9
更新日期:2015-06-04 00:00:00
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 previous...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2156
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS:BC mutation carrier cases from...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01341-3
更新日期:2020-10-21 00:00:00
abstract::The ductal approach to breast cancer, encompassing nipple aspiration, ductal lavage and duct endoscopy, allows assessment of breast ductal epithelial cells and their local microenvironment in a graded process of increasing invasiveness. Samples of ductal epithelial cells sufficient for cytological diagnosis may be saf...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr759
更新日期:2004-01-01 00:00:00
abstract::Proteins belonging to the profilin family of actin-binding proteins are considered to be important control elements for actin polymerization and have been linked to a broad spectrum of cellular functions, including cell migration. An intriguing paper recently published in Cancer Cell unveils differential effects of pr...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3433
更新日期:2013-06-27 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::Two articles previously published in Breast Cancer Research illustrate the high rates of breast cancer in Marin County, a wealthy, urban county immediately northwest of the city of San Francisco. I herein comment on these articles, and on the political/psychological/scientific dilemma presented by regions with high ca...
journal_title:Breast cancer research : BCR
pub_type: 评论,杂志文章,评审
doi:10.1186/bcr633
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Although aberrant tyrosine kinase signalling characterises particular breast cancer subtypes, a global analysis of tyrosine phosphorylation in mouse models of breast cancer has not been undertaken to date. This may identify conserved oncogenic pathways and potential therapeutic targets. METHODS:We applied...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-014-0437-3
更新日期:2014-09-09 00:00:00
abstract:INTRODUCTION:In response to gamma-irradiation (IR)-induced double-strand DNA breaks, cells undergo cell-cycle arrest, allowing time for DNA repair before reentering the cell cycle. G2/M checkpoint activation involves activation of ataxia telangiectasia mutated (ATM)/ATM- and rad3-related (ATR) kinases and inhibition of...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3164
更新日期:2012-04-11 00:00:00
abstract:INTRODUCTION:Reliable predictive and prognostic markers for routine diagnostic purposes are needed for breast cancer patients treated with neoadjuvant chemotherapy. We evaluated protein biomarkers in a cohort of 116 participants of the GeparDuo study on anthracycline/taxane-based neoadjuvant chemotherapy for operable b...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/bcr2363
更新日期:2009-01-01 00:00:00
abstract::Array-based comparative genomic hybridization, RNA expression profiling, and proteomic analyses are new molecular technologies used to study breast cancer. Invasive breast cancers were originally evaluated because they provided ample quantities of DNA, RNA, and protein. The application of these technologies to pre-inv...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr655
更新日期:2003-01-01 00:00:00
abstract::The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critica...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr1653
更新日期:2007-01-01 00:00:00