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Gene-expression Profiles To Predict Distant Metastasis Of Lymph-node-negative Primary Breast Cancer

Y. Wang, J. Klijn, Y. Zhang, A. Sieuwerts, J. Foekens
Published 2005 · Medicine

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BACKGROUND Genome-wide measures of gene expression can identify patterns of gene activity that subclassify tumours and might provide a better means than is currently available for individual risk assessment in patients with lymph-node-negative breast cancer. METHODS We analysed, with Affymetrix Human U133a GeneChips, the expression of 22000 transcripts from total RNA of frozen tumour samples from 286 lymph-node-negative patients who had not received adjuvant systemic treatment. FINDINGS In a training set of 115 tumours, we identified a 76-gene signature consisting of 60 genes for patients positive for oestrogen receptors (ER) and 16 genes for ER-negative patients. This signature showed 93% sensitivity and 48% specificity in a subsequent independent testing set of 171 lymph-node-negative patients. The gene profile was highly informative in identifying patients who developed distant metastases within 5 years (hazard ratio 5.67 [95% CI 2.59-12.4]), even when corrected for traditional prognostic factors in multivariate analysis (5.55 [2.46-12.5]). The 76-gene profile also represented a strong prognostic factor for the development of metastasis in the subgroups of 84 premenopausal patients (9.60 [2.28-40.5]), 87 postmenopausal patients (4.04 [1.57-10.4]), and 79 patients with tumours of 10-20 mm (14.1 [3.34-59.2]), a group of patients for whom prediction of prognosis is especially difficult. INTERPRETATION The identified signature provides a powerful tool for identification of patients at high risk of distant recurrence. The ability to identify patients who have a favourable prognosis could, after independent confirmation, allow clinicians to avoid adjuvant systemic therapy or to choose less aggressive therapeutic options.
This paper references
10.1016/S0140-6736(97)11423-4
Tamoxifen for early breast cancer: An overview of the randomised trials
O. Abe (1998)
10.1186/bcr433
Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer
C. Sotiriou (2001)
10.1016/S1043-321X(99)92039-8
Tamoxifen for early breast cancer: An overview of the randomised trials
D. Tripathy (1999)
10.1093/ANNONC/MDI326
Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005.
A. Goldhirsch (2005)
10.1093/oxfordjournals.jncimonographs.a003460
National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer, November 1-3, 2000.
P. Eifel (2001)
10.1056/NEJMOA021153
Cyclin E and survival in patients with breast cancer.
K. Keyomarsi (2002)
10.1038/4447
High density synthetic oligonucleotide arrays
R. Lipshutz (1999)
10.1016/S0140-6736(03)14686-7
Predictive ability of DNA microarrays for cancer outcomes and correlates: an empirical assessment
E. Ntzani (2003)
10.1073/pnas.1732912100
Breast cancer classification and prognosis based on gene expression profiles from a population-based study
C. Sotiriou (2003)
Polychemotherapy for early breast cancer: an overview of the randomised trials
M. Clarke (1998)
10.1093/JNCI/93.13.979
National Institutes of Health Consensus Development Conference statement: adjuvant therapy for breast cancer, November 1-3, 2000.
P. Eifel (2001)
www.thelancet.com Vol
(2005)
10.1006/EXMP.1999.2251
Adhesion proteins in the biology of breast cancer: contribution of CD44.
A. Herrera-Gayol (1999)
10.1038/35021093
Molecular portraits of human breast tumours
C. Perou (2000)
10.1073/pnas.0931261100
Gene expression profiles of human breast cancer progression
X. Ma (2003)
10.1016/S0140-6736(98)03301-7
Polychemotherapy for early breast cancer: an overview of the randomised trials
Early Breast Cancer Trialists' Collaborative Group (1998)
10.1038/415530a
Gene expression profiling predicts clinical outcome of breast cancer
L. J. Veer (2002)
10.1016/S0140-6736(02)07337-3
Identification of high risk breast-cancer patients by gene expression profiling
A. Ahr (2002)
10.1038/nrc1322
Rules of evidence for cancer molecular-marker discovery and validation
D. Ransohoff (2004)
Prognostic value of estrogen and progesterone receptors measured by enzyme immunoassays in human breast tumor cytosols.
J. Foekens (1989)
10.1056/nejm199511303332202
EFFECTS OF RADIOTHERAPY AND SURGERY IN EARLY BREAST-CANCER - AN OVERVIEW OF THE RANDOMIZED TRIALS
M. Clarke (1995)
10.1073/pnas.191367098
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
T. Sørlie (2001)
10.1200/JCO.2003.04.576
Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer.
A. Goldhirsch (2003)
10.1080/01621459.1981.10477650
Censored Data and the Bootstrap
B. Efron (1981)
National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer
P Eifel (2000)
10.1038/ng1060
A molecular signature of metastasis in primary solid tumors
S. Ramaswamy (2003)
Prognostic value of receptors for insulin-like growth factor 1, somatostatin, and epidermal growth factor in human breast cancer.
J. Foekens (1989)
10.1016/S0140-6736(03)14023-8
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer
J. Chang (2003)
Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns.
S. Gruvberger (2001)
10.1056/nejm199604113341522
Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials.
A. Howell (1995)
10.1073/pnas.0932692100
Repeated observation of breast tumor subtypes in independent gene expression data sets
T. Sørlie (2003)
10.1016/S0140-6736(03)13308-9
Gene expression predictors of breast cancer outcomes
E. Huang (2003)
10.1007/978-1-4612-4380-9_25
Nonparametric Estimation from Incomplete Observations
E. L. Kaplan (1958)
Molecular signature associated with bone marrow micrometastasis in human breast cancer.
U. Wölfle (2003)
10.1111/j.1532-5415.1988.tb02362.x
National Institutes of Health Consensus Development Conference Statement: Geriatric Assessment Methods for Clinical Decision‐making
A. Brown (1988)
A Gene-Expression Signature as a Predictor of Survival in Breast Cancer
J. (2002)
10.1056/NEJM200102223440801
Gene-expression profiles in hereditary breast cancer.
I. Hedenfalk (2001)
10.1200/JCO.2004.08.186
Gene expression profiles and molecular markers to predict recurrence of Dukes' B colon cancer.
Y. Wang (2004)



This paper is referenced by
10.1098/rstb.2012.0363
Deconvoluting complex tissues for expression quantitative trait locus-based analyses
Ji-Heui Seo (2013)
An Imaging-based RNA-Interference Migration Screen Identifies the Splicing Related SRSF Protein Kinase 1 (SRPK1) as a Clinical Relevant Breast Cancer Metastasis Promoter
van Roosmalen (2012)
10.1038/nm1764
Stromal gene expression predicts clinical outcome in breast cancer
Greg Finak (2008)
10.1080/00313020500169586
Gene expression profiling in breast cancer: towards individualising patient management
N. Murphy (2005)
10.1200/JCO.2005.03.9792
Genomic profiling of cancer: what next?
P. Workman (2005)
10.1200/JCO.2005.03.3845
Molecular classification and molecular forecasting of breast cancer: ready for clinical application?
J. Brenton (2005)
10.1186/bcr1205
The role of gene expression profiling by microarray analysis for prognostic classification of breast cancer
M. V. D. Vijver (2005)
10.1007/s10549-014-3098-0
Phosphorylation of activating transcription factor-2 (ATF-2) within the activation domain is a key determinant of sensitivity to tamoxifen in breast cancer
B. Rudraraju (2014)
10.1186/gb-2013-14-1-r6
Genome-wide mapping of FOXM1 binding reveals co-binding with estrogen receptor alpha in breast cancer cells
Deborah A. Sanders (2012)
10.18632/oncotarget.8029
Geminin overexpression-dependent recruitment and crosstalk with mesenchymal stem cells enhance aggressiveness in triple negative breast cancers
Suryatheja Ananthula (2016)
10.1038/nrclinonc.2010.134
Future directions of bone-targeted therapy for metastatic breast cancer
Tomifumi Onishi (2010)
10.1016/j.ccr.2011.05.026
Targeting androgen receptor in estrogen receptor-negative breast cancer.
M. Ni (2011)
10.1016/S1533-0028(11)70238-9
Clinical utility of gene microarray for the management of colorectal cancer.
A. D'Orazio (2006)
10.1111/bdi.12005
State‐related alterations of gene expression in bipolar disorder: a systematic review
Klaus Munkholm (2012)
10.1242/jcs.198200
ADAM12 induction by Twist1 promotes tumor invasion and metastasis via regulation of invadopodia and focal adhesions
M. Eckert (2017)
10.1158/1078-0432.CCR-06-2433
Poor Outcome in Estrogen Receptor–Positive Breast Cancers Predicted by Loss of Plexin B1
A. Rody (2007)
10.1186/gb-2006-7-12-r117
Dissection of a metastatic gene expression signature into distinct components
P. Roepman (2006)
10.1007/978-1-59745-390-5_7
Gene expression profiles and prognostic markers for primary breast cancer.
Y. Wang (2007)
10.1186/bcr1614
Predicting a local recurrence after breast-conserving therapy by gene expression profiling
D. Nuyten (2006)
Die prognostische Relevanz des primären axillären Lymphknotenstatus beim Rezidiv des Mammakarzinoms
K. Friese (2008)
10.1007/978-0-387-73161-2_
Advances in adjuvant chemotherapy of early stage breast cancer.
H. McArthur (2008)
10.1007/978-0-387-79251-4_2
Biomarkers in Schizophrenia
A. Wong (2008)
10.1007/s10549-007-9594-8
HER2 expression and efficacy of preoperative paclitaxel/FAC chemotherapy in breast cancer
F. André (2007)
10.1051/MEDSCI/20082467599
Classification pronostique du cancer du sein et profils d’expression génique sur puces à ADN
F. Bertucci (2008)
10.1016/j.canlet.2008.07.014
Effective stimulation of growth in MCF-7 human breast cancer cells by inhibition of syntaxin18 by external guide sequence and ribonuclease P.
T. Bassett (2008)
10.1016/j.ccr.2008.11.013
MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer.
G. Hu (2009)
10.1111/j.1582-4934.2009.00906.x
Genetic characterization of breast cancer and implications for clinical management
F. Geyer (2009)
10.1038/sj.bjc.6605423
CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer
T. van Agthoven (2009)
10.1016/S0001-4079(19)32378-7
Évaluation immunohistochimique du risque métastasique dans les cancers du sein débutants sur microbiopsies
Colette Taranger-Charpin (2009)
10.1007/978-1-4419-6615-5_13
Bone Marrow Derived Mesenchymal Stem/Stromal Cells and Tumor Growth
Pravin J. Mishra (2010)
Algorithms for discovery of multiple markov boundaries: application to the molecular signature multiplicity problem
C. Aliferis (2008)
10.1097/PDM.0b013e3181831320
Reliability and Reproducibility of a RNA Preamplification Method for Low-density Array Analysis From Formalin-fixed Paraffin-embedded Breast Cancer Samples
P. Ciotti (2009)
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