Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. Export

@article{citeulike:1052799, abstract = {BACKGROUND: Histologic grade in breast cancer provides clinically important prognostic information. However, 30\%-60\% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profiles of breast cancers and whether such profiles could be used to improve histologic grading. METHODS: We analyzed microarray data from 189 invasive breast carcinomas and from three published gene expression datasets from breast carcinomas. We identified differentially expressed genes in a training set of 64 estrogen receptor (ER)-positive tumor samples by comparing expression profiles between histologic grade 3 tumors and histologic grade 1 tumors and used the expression of these genes to define the gene expression grade index. Data from 597 independent tumors were used to evaluate the association between relapse-free survival and the gene expression grade index in a Kaplan-Meier analysis. All statistical tests were two-sided. RESULTS: We identified 97 genes in our training set that were associated with histologic grade; most of these genes were involved in cell cycle regulation and proliferation. In validation datasets, the gene expression grade index was strongly associated with histologic grade 1 and 3 status; however, among histologic grade 2 tumors, the index spanned the values for histologic grade 1-3 tumors. Among patients with histologic grade 2 tumors, a high gene expression grade index was associated with a higher risk of recurrence than a low gene expression grade index (hazard ratio = 3.61, 95\% confidence interval = 2.25 to 5.78; P < .001, log-rank test). CONCLUSIONS: Gene expression grade index appeared to reclassify patients with histologic grade 2 tumors into two groups with high versus low risks of recurrence. This approach may improve the accuracy of tumor grading and thus its prognostic value.}, address = {Functional Genomics and Translational Research Unit, Universit\'{e} Libre de Bruxelles, Brussels, Belgium. christos.sotiriou@bordet.be}, author = {Sotiriou, Christos and Wirapati, Pratyaksha and Loi, Sherene and Harris, Adrian and Fox, Steve and Smeds, Johanna and Nordgren, Hans and Farmer, Pierre and Praz, Viviane and Haibe-Kains, Benjamin and Desmedt, Christine and Larsimont, Denis and Cardoso, Fatima and Peterse, Hans and Nuyten, Dimitry and Buyse, Marc and Van de Vijver, Marc J. and Bergh, Jonas and Piccart, Martine and Delorenzi, Mauro}, citeulike-article-id = {1052799}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/jnci/djj052}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16478745}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16478745}, day = {15}, doi = {10.1093/jnci/djj052}, issn = {1460-2105}, journal = {Journal of the National Cancer Institute}, keywords = {aggressiveness, basis, breast, cancer, grade, histologic, molecular, thelist}, month = {February}, number = {4}, pages = {262--272}, posted-at = {2009-04-08 20:15:55}, priority = {2}, title = {Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.}, url = {http://dx.doi.org/10.1093/jnci/djj052}, volume = {98}, year = {2006} }

TY - JOUR ID - citeulike:1052799 L3 - citeulike-article-id:1052799 N2 - BACKGROUND: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profiles of breast cancers and whether such profiles could be used to improve histologic grading. METHODS: We analyzed microarray data from 189 invasive breast carcinomas and from three published gene expression datasets from breast carcinomas. We identified differentially expressed genes in a training set of 64 estrogen receptor (ER)-positive tumor samples by comparing expression profiles between histologic grade 3 tumors and histologic grade 1 tumors and used the expression of these genes to define the gene expression grade index. Data from 597 independent tumors were used to evaluate the association between relapse-free survival and the gene expression grade index in a Kaplan-Meier analysis. All statistical tests were two-sided. RESULTS: We identified 97 genes in our training set that were associated with histologic grade; most of these genes were involved in cell cycle regulation and proliferation. In validation datasets, the gene expression grade index was strongly associated with histologic grade 1 and 3 status; however, among histologic grade 2 tumors, the index spanned the values for histologic grade 1-3 tumors. Among patients with histologic grade 2 tumors, a high gene expression grade index was associated with a higher risk of recurrence than a low gene expression grade index (hazard ratio = 3.61, 95% confidence interval = 2.25 to 5.78; P < .001, log-rank test). CONCLUSIONS: Gene expression grade index appeared to reclassify patients with histologic grade 2 tumors into two groups with high versus low risks of recurrence. This approach may improve the accuracy of tumor grading and thus its prognostic value. IS - 4 JF - Journal of the National Cancer Institute SN - 1460-2105 AD - Functional Genomics and Translational Research Unit, Université Libre de Bruxelles, Brussels, Belgium. christos.sotiriou@bordet.be EP - 272 TI - Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. VL - 98 SP - 262 KW - aggressiveness KW - basis KW - breast KW - cancer KW - grade KW - histologic KW - molecular KW - thelist AU - Sotiriou, Christos AU - Wirapati, Pratyaksha AU - Loi, Sherene AU - Harris, Adrian AU - Fox, Steve AU - Smeds, Johanna AU - Nordgren, Hans AU - Farmer, Pierre AU - Praz, Viviane AU - Haibe-Kains, Benjamin AU - Desmedt, Christine AU - Larsimont, Denis AU - Cardoso, Fatima AU - Peterse, Hans AU - Nuyten, Dimitry AU - Buyse, Marc AU - Van de Vijver, Marc AU - Bergh, Jonas AU - Piccart, Martine AU - Delorenzi, Mauro PY - 2006/02/15/ UR - http://dx.doi.org/10.1093/jnci/djj052 ER -