Journal ArticleDOI
A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer
Soonmyung Paik,Steven Shak,Gong Tang,Chungyeul Kim,Joffre B. Baker,Maureen T. Cronin,Frederick L. Baehner,Michael G. Walker,Drew Watson,Taesung Park,William Hiller,Edwin R. Fisher,D. Lawrence Wickerham,John Bryant,Norman Wolmark +14 more
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TLDR
The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer and could be used as a continuous function to predict distant recurrent in individual patients.Abstract:
background The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor–positive tumors is poorly defined by clinical and histopathological measures. methods We tested whether the results of a reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancerrelated genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. results Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan–Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. conclusions The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor–positive breast cancer.read more
Citations
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Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades
Laura J. Esserman,Christina Yau,Christina Yau,Carlie K Thompson,Laura J. van't Veer,Alexander D. Borowsky,Katherine A. Hoadley,Nicholas P. Tobin,Bo Nordenskjöld,Tommy Fornander,Olle Stål,Christopher C. Benz,Christopher C. Benz,Linda S. Lindström +13 more
TL;DR: The ultralow-risk threshold of the 70-gene MammaPrint assay can identify patients whose long-term systemic risk of death from breast cancer after surgery alone is exceedingly low.
Journal ArticleDOI
Tumour biomarker expression relative to age and molecular subtypes of invasive breast cancer
TL;DR: It is demonstrated that molecular subtype defined by IHC was an independent prognostic factor in invasive breast cancer and survival difference among subtypes was demonstrated by multivariate analysis.
Journal ArticleDOI
Cancer therapy trials employing level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1.
Manfred Schmitt,Nadia Harbeck,Nils Brünner,Fritz Jänicke,Christoph Meisner,Bernd Mühlenweg,Heike Jansen,Julia Dorn,Ulrike Nitz,Eva Johanna Kantelhardt,Christoph Thomssen +10 more
TL;DR: Light is shed on the current status of major clinical Phase II and III breast cancer therapy trials (Chemo-N0, NNBC-3 and Plan B), and ongoing clinical trials targeting uPA in advanced cancers of the breast and pancreas, employing synthetic small-size drugs to counteract uPA activity.
Journal ArticleDOI
Health literacy and cancer risk perception: implications for genomic risk communication.
Noel T. Brewer,Janice P. Tzeng,Sarah E. Lillie,Alrick S. Edwards,Jeffrey Peppercorn,Barbara K. Rimer +5 more
TL;DR: The greater variability in responding by women with lower health literacy supports the hypothesis that they have less precise mental representations of risk, but more research is needed to rule out other possible explanations.
Journal ArticleDOI
Molecular profiling currently offers no more than tumour morphology and basic immunohistochemistry.
TL;DR: Despite the huge amount of resources allocated to translational research endeavours, only three predictive markers are utilised to define the therapy of breast cancer patients: oestrogen receptor and progesterone receptor (PR), the predictive markers of response to endocrine therapy, and human epidermal growth factor receptor 2 (HER2), the molecular target of trastuzumab and lapatinib.
References
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Journal ArticleDOI
Molecular portraits of human breast tumours
Charles M. Perou,Therese Sørlie,Michael B. Eisen,Matt van de Rijn,Stefanie S. Jeffrey,Christian A. Rees,Jonathan R. Pollack,Douglas T. Ross,Hilde Johnsen,Lars A. Akslen,Øystein Fluge,Alexander Pergamenschikov,Cheryl A. Williams,Shirley Zhu,Per Eystein Lønning,Anne Lise Børresen-Dale,Patrick O. Brown,David Botstein +17 more
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Molecular classification of cancer: class discovery and class prediction by gene expression monitoring.
Todd R. Golub,Todd R. Golub,Donna K. Slonim,Pablo Tamayo,Christine Huard,Michelle Gaasenbeek,Jill P. Mesirov,Hilary A. Coller,Mignon L. Loh,James R. Downing,Michael A. Caligiuri,Clara D. Bloomfield,Eric S. Lander +12 more
TL;DR: A generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case and suggests a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.
Journal ArticleDOI
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
Therese Sørlie,Charles M. Perou,Robert Tibshirani,Turid Aas,Stephanie Geisler,Hilde Johnsen,Trevor Hastie,Michael B. Eisen,Matt van de Rijn,Stefanie S. Jeffrey,T. Thorsen,Hanne Quist,John C. Matese,Patrick O. Brown,David Botstein,Per Eystein Lønning,Anne Lise Børresen-Dale +16 more
TL;DR: Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.
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Quantitative monitoring of gene expression patterns with a complementary DNA microarray.
TL;DR: A high-capacity system was developed to monitor the expression of many genes in parallel by means of simultaneous, two-color fluorescence hybridization, which enabled detection of rare transcripts in probe mixtures derived from 2 micrograms of total cellular messenger RNA.
Journal ArticleDOI
Gene expression profiling predicts clinical outcome of breast cancer
Laura J. van't Veer,Hongyue Dai,Marc J. van de Vijver,Yudong D. He,Augustinus A. M. Hart,Mao Mao,Hans Peterse,Karin van der Kooy,Matthew J. Marton,Anke T. Witteveen,George J. Schreiber,Ron M. Kerkhoven,Christopher J. Roberts,Peter S. Linsley,René Bernards,Stephen H. Friend +15 more
TL;DR: DNA microarray analysis on primary breast tumours of 117 young patients is used and supervised classification is applied to identify a gene expression signature strongly predictive of a short interval to distant metastases (‘poor prognosis’ signature) in patients without tumour cells in local lymph nodes at diagnosis, providing a strategy to select patients who would benefit from adjuvant therapy.
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