A Gene-Expression Signature as a Predictor of Survival in Breast Cancer
Marc J. van de Vijver, M.D., Ph.D., Yudong D. He, Ph.D., Laura J. van 't Veer, Ph.D., Hongyue Dai, Ph.D., Augustinus A.M. Hart, M.Sc., Dorien W. Voskuil, Ph.D., George J. Schreiber, M.Sc., Johannes L. Peterse, M.D., Chris Roberts, Ph.D., Matthew J. Marton, Ph.D., Mark Parrish, Douwe Atsma, Anke Witteveen, Annuska Glas, Ph.D., Leonie Delahaye, Tony van der Velde, Harry Bartelink, M.D., Ph.D., Sjoerd Rodenhuis, M.D., Ph.D., Emiel T. Rutgers, M.D., Ph.D., Stephen H. Friend, M.D., Ph.D., and René Bernards, Ph.D.
Background A more accurate means of prognostication in breastcancer will improve the selection of patients for adjuvant systemictherapy.
Methods Using microarray analysis to evaluate our previouslyestablished 70-gene prognosis profile, we classified a seriesof 295 consecutive patients with primary breast carcinomas ashaving a gene-expression signature associated with either apoor prognosis or a good prognosis. All patients had stage Ior II breast cancer and were younger than 53 years old; 151had lymph-nodenegative disease, and 144 had lymph-nodepositivedisease. We evaluated the predictive power of the prognosisprofile using univariable and multivariable statistical analyses.
Conclusions The gene-expression profile we studied is a morepowerful predictor of the outcome of disease in young patientswith breast cancer than standard systems based on clinical andhistologic criteria.
Source Information
From the Divisions of Diagnostic Oncology (M.J.V., L.J.V., D.W.V., J.L.P., D.A., A.W., A.G., L.D.), Radiotherapy (A.A.M.H., H.B.), Medical Oncology (S.R.), Biometrics (T.V.), Surgical Oncology (E.T.R.), and Molecular Carcinogenesis (R.B.), Netherlands Cancer Institute, Amsterdam; the Center for Biomedical Genetics, Amsterdam (R.B.); and Rosetta Inpharmatics, Kirkland, Wash. (Y.D.H., H.D., G.J.S., C.R., M.J.M., M.P., S.H.F.). Drs. van de Vijver, He, and van 't Veer contributed equally to this article.
Address reprint requests to Dr. Bernards at the Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands, or at r.bernards{at}nki.nl.
Gene-Expression Signatures in Breast Cancer
Helmbold P., Haerting J., Kölbl H., Kopans D. B., Kunkler I. H., Ransohoff D. F., van de Vijver M. J., He Y. D., van 't Veer L. J., Bernards R.
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N Engl J Med 2003;
348:1715-1717, Apr 24, 2003.
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Landemaine, T., Jackson, A., Bellahcene, A., Rucci, N., Sin, S., Abad, B. M., Sierra, A., Boudinet, A., Guinebretiere, J.-M., Ricevuto, E., Nogues, C., Briffod, M., Bieche, I., Cherel, P., Garcia, T., Castronovo, V., Teti, A., Lidereau, R., Driouch, K.
(2008). A Six-Gene Signature Predicting Breast Cancer Lung Metastasis. Cancer Res.
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Han, Y., Yang, L., Suarez-Saiz, F., San-Marina, S., Cui, J., Minden, M. D.
(2008). Wilms' Tumor 1 Suppressor Gene Mediates Antiestrogen Resistance via Down-Regulation of Estrogen Receptor-{alpha} Expression in Breast Cancer Cells. Mol Cancer Res
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Sturgeon, C. M., Hoffman, B. R., Chan, D. W., Ch'ng, S.-L., Hammond, E., Hayes, D. F., Liotta, L. A., Petricoin, E. F., Schmitt, M., Semmes, O. J., Soletormos, G., van der Merwe, E., Diamandis, E. P.
(2008). National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality Requirements. Clin. Chem.
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Turner, N. C, Jones, A. L
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Anders, C. K., Hsu, D. S., Broadwater, G., Acharya, C. R., Foekens, J. A., Zhang, Y., Wang, Y., Marcom, P. K., Marks, J. R., Febbo, P. G., Nevins, J. R., Potti, A., Blackwell, K. L.
(2008). Young Age at Diagnosis Correlates With Worse Prognosis and Defines a Subset of Breast Cancers With Shared Patterns of Gene Expression. JCO
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Ellsworth, R. E., Ellsworth, D. L., Patney, H. L., Deyarmin, B., Hooke, J. A., Love, B., Shriver, C. D.
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Colman, H., Aldape, K.
(2008). Molecular Predictors in Glioblastoma: Toward Personalized Therapy. Arch Neurol
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Schmidt, M., Bohm, D., von Torne, C., Steiner, E., Puhl, A., Pilch, H., Lehr, H.-A., Hengstler, J. G., Kolbl, H., Gehrmann, M.
(2008). The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer. Cancer Res.
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Singh, B., Pfister, D. G.
(2008). Individualized Treatment Selection in Patients With Head and Neck Cancer: Do Molecular Markers Meet the Challenge?. JCO
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Grube, B. J., Christy, C. J., Black, D., Martel, M., Harris, L., Weidhaas, J., DiGiovanna, M. P., Chung, G., Abu-Khalaf, M. M., Miller, K. D., Higgins, S. A., Philpotts, L., Tavassoli, F. A., Lannin, D. R.
(2008). Breast Sentinel Lymph Node Dissection Before Preoperative Chemotherapy. Arch Surg
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Jiang, Y., Casey, G., Lavery, I. C., Zhang, Y., Talantov, D., Martin-McGreevy, M., Skacel, M., Manilich, E., Mazumder, A., Atkins, D., Delaney, C. P., Wang, Y.
(2008). Development of a Clinically Feasible Molecular Assay to Predict Recurrence of Stage II Colon Cancer. J. Mol. Diagn.
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Nam, D.-H., Jeon, H.-M., Kim, S., Kim, M. H., Lee, Y.-J., Lee, M. S., Kim, H., Joo, K. M., Lee, D.-S., Price, J. E., Bang, S. I., Park, W.-Y.
(2008). Activation of Notch Signaling in a Xenograft Model of Brain Metastasis. Clin. Cancer Res.
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Diomedi-Camassei, F., McDowell, H. P., De Ioris, M. A., Uccini, S., Altavista, P., Raschella, G., Vitali, R., Mannarino, O., De Sio, L., Cozzi, D. A., Donfrancesco, A., Inserra, A., Callea, F., Dominici, C.
(2008). Clinical Significance of CXC Chemokine Receptor-4 and c-Met in Childhood Rhabdomyosarcoma. Clin. Cancer Res.
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Glinsky, G. V.
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Weinberg, R. A.
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Sauer, G., Schneiderhan-Marra, N., Kazmaier, C., Hutzel, K., Koretz, K., Muche, R., Kreienberg, R., Joos, T., Deissler, H.
(2008). Prediction of Nodal Involvement in Breast Cancer Based on Multiparametric Protein Analyses from Preoperative Core Needle Biopsies of the Primary Lesion. Clin. Cancer Res.
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Winnard, P. T. Jr., Pathak, A. P., Dhara, S., Cho, S. Y., Raman, V., Pomper, M. G.
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Wittner, B. S., Sgroi, D. C., Ryan, P. D., Bruinsma, T. J., Glas, A. M., Male, A., Dahiya, S., Habin, K., Bernards, R., Haber, D. A., Van't Veer, L. J., Ramaswamy, S.
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Dieterich, C., Iglehart, D., Riccio, E., Mirsalis, J. C., Ng, H. H.
(2008). Microarray Evaluation of the Listeria monocytogenes Infection and Amoxicillin Treatment in Mice. International Journal of Toxicology
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Barnett, D. H., Sheng, S., Howe Charn, T., Waheed, A., Sly, W. S., Lin, C.-Y., Liu, E. T., Katzenellenbogen, B. S.
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