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 vascular endothelial growth factor (VEGF) family members in high-risk early breast cancer patients treated with adjuvant chemo-hormonotherapy. METHODS:RNA was isolated from 308 formalin-fixed paraffin-embedded primary tumor samples from breast cancer patients enrolled in the HE10/97 trial, evaluating adjuvant dose-dense sequential chemotherapy with epirubicin followed by cyclophosphamide, methotrexate, fluorouracil (CMF) with or without paclitaxel (E-T-CMF versus E-CMF). A fully automated method based on magnetic beads was applied for RNA extraction, followed by one-step quantitative RT-PCR for mRNA analysis of VEGF-A, -B, -C and vascular endothelial growth factor receptor (VEGFR) 1, 2, 3. RESULTS:With a median follow-up of 8 years, 109 patients (35%) developed a relapse and 80 patients (26%) died. In high VEGF-C and VEGFR1 mRNA expressing tumors, ER/PgR-negative tumors (Fisher's exact test, P = 0.001 and P = 0.021, respectively) and HER2-positive tumors (P <0.001 and P = 0.028, respectively) were more frequent than in low VEGF-C and VEGFR1 expressing tumors, respectively. From the VEGF family members evaluated, high VEGFR1 mRNA expression (above the 75th percentile) emerged as a significant negative prognostic factor for overall survival (OS; hazard ratio (HR) = 1.60, 95% confidence interval (CI): 1.01 to 2.55, Wald's P = 0.047) and disease-free survival (DFS; HR = 1.67, 95% CI: 1.13 to 2.48, P = 0.010), when adjusting for treatment group. High VEGF-C mRNA expression was predictive for benefit from adjuvant treatment with paclitaxel (E-T-CMF arm) for OS (test for interaction, Wald's P = 0.038), while in multivariate analysis the interaction of VEGF-C with taxane treatment was significant for both OS (Wald's P = 0.019) and DFS (P = 0.041) and continuous VEGF-B mRNA expression values for OS (P = 0.019). CONCLUSIONS:The present study reports, for the first time, that VEGF-C mRNA overexpression, as assessed by qRT-PCR, has a strong predictive value in high-risk early breast cancer patients undergoing adjuvant paclitaxel-containing treatment. Further studies are warranted to validate the prognostic and/or predictive value of VEGF-B, VEGF-C and VEGFR1 in patients treated with adjuvant therapies and to reveal which members of the VEGF family could possibly be useful markers in identifying patients who will benefit most from anti-VEGF strategies. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12611000506998.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Linardou H,Kalogeras KT,Kronenwett R,Kouvatseas G,Wirtz RM,Zagouri F,Gogas H,Christodoulou C,Koutras AK,Samantas E,Pectasides D,Bafaloukos D,Fountzilas Gdoi
10.1186/bcr3354subject
Has Abstractpub_date
2012-11-12 00:00:00pages
R145issue
6eissn
1465-5411issn
1465-542Xpii
bcr3354journal_volume
14pub_type
杂志文章,随机对照试验abstract:INTRODUCTION:Isoflavones are hypothesized to protect against breast cancer, but it is not clear whether they act as oestrogens or anti-oestrogens in breast tissue. Our aim was to determine the effects of taking a red clover-derived isoflavone supplement daily for 1 year on mammographic breast density. Effects on oestra...
journal_title:Breast cancer research : BCR
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1186/bcr773
更新日期:2004-01-01 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:This study was designed to determine if and how a non-toxic, naturally occurring bioflavonoid, galangin, affects proliferation of human mammary tumor cells. Our previous studies demonstrated that, in other cell types, galangin is a potent inhibitor of the aryl hydrocarbon receptor (AhR), an environmental c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1391
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Women with breast cancer who have multiple affected relatives are more likely to have inherited genetic risk factors for the disease. All the currently known genetic risk factors for breast cancer account for less than half of the average familial risk. Furthermore, the genetic factor(s) underlying an increa...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0825-6
更新日期:2017-03-16 00:00:00
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 patt...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1512
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:Laboratory and epidemiologic studies have suggested a modifying effect of cardiac glycosides (for example, digoxin and digitoxin) on cancer risk. We explored the association between digoxin treatment and invasive breast cancer incidence among postmenopausal Danish women. METHODS:We used Danish registries ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2205
更新日期:2008-01-01 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::HER2 amplification and overexpression is observed in approximately 20% of breast cancers and is strongly associated with poor prognosis and therapeutic responsiveness to HER2 targeted agents. A recent study by Bose and colleagues suggests that another subset of breast cancer patients without HER2 amplification but wit...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3406
更新日期:2013-04-23 00:00:00
abstract:INTRODUCTION:Estrogens play a pivotal role in the initiation and progression of breast cancer. The genes that mediate these processes are not fully defined, but potentially include the known mammary oncogene MYC. Characterization of estrogen-target genes may help to elucidate further the mechanisms of estrogen-induced ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1985
更新日期:2008-01-01 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::Many women newly diagnosed with breast cancer and with a strong family history of breast cancer are referred to a family cancer service for genetic counselling and for consideration of genetic testing for germline mutations in cancer predisposition genes following completion of their cancer treatment. However, there i...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr2194
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:The amplification event occurring at chromosome locus 11q13, reported in several different cancers, includes a number of potential oncogenes. We have previously reported amplification of one such oncogene, namely CCND1, to be correlated with an adverse effect of tamoxifen in premenopausal breast cancer pat...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2150
更新日期:2008-01-01 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: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:Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Ca...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3627
更新日期:2014-03-17 00:00:00
abstract::In recent years it has become clear that cancer cells within a single tumor can display striking morphological, genetic and behavioral variability. Burgeoning genetic, epigenetic and phenomenological data support the existence of intra-tumor genetic heterogeneity in breast cancers; however, its basis is yet to be full...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr3658
更新日期:2014-05-20 00:00:00
abstract:INTRODUCTION:The re-emergence of the tumour growth factor-beta (TGF-beta)-related embryonic morphogen Nodal has recently been reported in several different human cancers. In this study, we examined the expression of Nodal in a series of benign and malignant human breast tissues to determine the clinical significance of...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3185
更新日期:2012-05-11 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::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: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::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:The HER (human EGFR related) family of receptor tyrosine kinases (HER1/EGFR (epidermal growth factor receptor)/c-erbB1, HER2/c-erbB2, HER3/c-erbB3 and HER4/c-erbB4) shares a high degree of structural and functional homology. It constitutes a complex network, coupling various extracellular ligands to intrac...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1843
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Protein tyrosine kinase 6 (PTK6) is a non-receptor tyrosine kinase that is highly expressed in Human Epidermal Growth Factor 2(+) (Her2(+)) breast cancers. Overexpression of PTK6 enhances anchorage-independent survival, proliferation, and migration of breast cancer cells. We hypothesized that PTK6 inhibiti...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0594-z
更新日期:2015-06-19 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 European Network for Breast Development and Cancer (ENBDC) Workshop on ‘Methods in Mammary Gland Development and Cancer’ has grown into the essential, international technical discussion forum for scientists with interests in the normal and neoplastic breast. The fifth ENBDC meeting was held in Weggis, Switzerland ...
journal_title:Breast cancer research : BCR
pub_type:
doi:10.1186/bcr3497
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Several anthropometric measures have been found to be associated with the risk of breast cancer. Current weight, body mass index, and adult weight gain appear to be predictors of postmenopausal breast cancer. These factors have been associated with a reduced risk of premenopausal breast cancer. We asked whet...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1293
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal wom...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1128-x
更新日期:2019-03-28 00:00:00
abstract::The adaptor protein NHERF1/EBP50 (Na/H exchanger regulatory factor 1/ezrin-radixin-moesin-binding phosphoprotein 50) emerged recently as an important player in breast cancer progression. Consisting of two tandem PDZ domains linked to a carboxyl-terminal ezrin-binding region, NHERF1 assembles macromolecular complexes a...
journal_title:Breast cancer research : BCR
pub_type: 评论,社论
doi:10.1186/bcr1992
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Cellular senescence is a terminal cell proliferation arrest that can be triggered by oncogenes. One of the traits of oncogene-induced senescence (OIS) is the so-called senescence-associated secretory phenotype or senescence secretome. Depending on the context, the non-cell autonomous effects of OIS may var...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0619-7
更新日期:2015-08-12 00:00:00
abstract::The potential for a reduction in dietary fat or for an increase in dietary fiber to reduce breast cancer risk has been debated for some years. It is argued here that available research data, even though extensive, leave open hypotheses ranging from little or no potential to major public health potential for breast can...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr68
更新日期:2000-01-01 00:00:00