TY - JOUR
T1 - Predicting features of breast cancer with gene expression patterns
AU - Lu, Xuesong
AU - Lu, Xin
AU - Wang, Zhigang C.
AU - Iglehart, J. Dirk
AU - Zhang, Xuegong
AU - Richardson, Andrea L.
N1 - Funding Information:
Acknowledgements Supported by the Breast Cancer Research Foundation (BCRF) and by the Dana-Faber/Harvard SPORE in Breast Cancer from the National Cancer Institute (J.D.I., A.R.), grants ACS-IRG 70-002 and CA23100-22 (X.L), NSFC grant 30625012 and the National Basic Research Program (2004CB518605) of China (X.Z.).
PY - 2008/3
Y1 - 2008/3
N2 - Data from gene expression arrays hold an enormous amount of biological information. We sought to determine if global gene expression in primary breast cancers contained information about biologic, histologic, and anatomic features of the disease in individual patients. Microarray data from the tumors of 129 patients were analyzed for the ability to predict biomarkers [estrogen receptor (ER) and HER2], histologic features [grade and lymphatic-vascular invasion (LVI)], and stage parameters (tumor size and lymph node metastasis). Multiple statistical predictors were used and the prediction accuracy was determined by cross-validation error rate; multidimensional scaling (MDS) allowed visualization of the predicted states under study. Models built from gene expression data accurately predict ER and HER2 status, and divide tumor grade into high-grade and low-grade clusters; intermediate-grade tumors are not a unique group. In contrast, gene expression data is inaccurate at predicting tumor size, lymph node status or LVI. The best model for prediction of nodal status included tumor size, LVI status and pathologically defined tumor subtype (based on combinations of ER, HER2, and grade); the addition of microarray-based prediction to this model failed to improve the prediction accuracy. Global gene expression supports a binary division of ER, HER2, and grade, clearly separating tumors into two categories; intermediate values for these bio-indicators do not define intermediate tumor subsets. Results are consistent with a model of regional metastasis that depends on inherent biologic differences in metastatic propensity between breast cancer subtypes, upon which time and chance then operate.
AB - Data from gene expression arrays hold an enormous amount of biological information. We sought to determine if global gene expression in primary breast cancers contained information about biologic, histologic, and anatomic features of the disease in individual patients. Microarray data from the tumors of 129 patients were analyzed for the ability to predict biomarkers [estrogen receptor (ER) and HER2], histologic features [grade and lymphatic-vascular invasion (LVI)], and stage parameters (tumor size and lymph node metastasis). Multiple statistical predictors were used and the prediction accuracy was determined by cross-validation error rate; multidimensional scaling (MDS) allowed visualization of the predicted states under study. Models built from gene expression data accurately predict ER and HER2 status, and divide tumor grade into high-grade and low-grade clusters; intermediate-grade tumors are not a unique group. In contrast, gene expression data is inaccurate at predicting tumor size, lymph node status or LVI. The best model for prediction of nodal status included tumor size, LVI status and pathologically defined tumor subtype (based on combinations of ER, HER2, and grade); the addition of microarray-based prediction to this model failed to improve the prediction accuracy. Global gene expression supports a binary division of ER, HER2, and grade, clearly separating tumors into two categories; intermediate values for these bio-indicators do not define intermediate tumor subsets. Results are consistent with a model of regional metastasis that depends on inherent biologic differences in metastatic propensity between breast cancer subtypes, upon which time and chance then operate.
KW - Breast cancer
KW - Computational molecular biology
KW - Gene expression profiling
KW - Metastasis
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U2 - 10.1007/s10549-007-9596-6
DO - 10.1007/s10549-007-9596-6
M3 - Article
C2 - 18297396
AN - SCOPUS:39749176127
SN - 0167-6806
VL - 108
SP - 191
EP - 201
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -