Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer.

@article{citeulike:281686, abstract = {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.}, address = {Veridex LLC, a Johnson \& Johnson Company, San Diego, CA, USA.}, author = {Wang, Y. and Klijn, J. G. and Zhang, Y. and Sieuwerts, A. M. and Look, M. P. and Yang, F. and Talantov, D. and Timmermans, M. and Meijer-van Gelder, M. E. and Yu, J. and Jatkoe, T. and Berns, E. M. and Atkins, D. and Foekens, J. A. }, citeulike-article-id = {281686}, doi = {http://dx.doi.org/10.1016/S0140-6736(05)17947-1}, issn = {1474-547X}, journal = {Lancet}, keywords = {cancer, microarray}, number = {9460}, pages = {671--679}, posted-at = {2008-06-09 16:32:02}, priority = {0}, title = {Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer.}, url = {http://dx.doi.org/10.1016/S0140-6736(05)17947-1}, volume = {365}, year = {2005} }

TY - JOUR ID - citeulike:281686 L3 - citeulike-article-id:281686 N2 - 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. IS - 9460 JF - Lancet SN - 1474-547X AD - Veridex LLC, a Johnson & Johnson Company, San Diego, CA, USA. EP - 679 TI - Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. VL - 365 SP - 671 KW - cancer KW - microarray AU - Wang, Y AU - Klijn, JG AU - Zhang, Y AU - Sieuwerts, AM AU - Look, MP AU - Yang, F AU - Talantov, D AU - Timmermans, M AU - Meijer-van Gelder, ME AU - Yu, J AU - Jatkoe, T AU - Berns, EM AU - Atkins, D AU - Foekens, JA PY - 2005///5 UR - http://dx.doi.org/10.1016/S0140-6736(05)17947-1 ER -