TY - JOUR
T1 - Limits of predictive models using microarray data for breast cancer clinical treatment outcome
AU - Reid, James F.
AU - Lusa, Lara
AU - De Cecco, Loris
AU - Coradini, Danila
AU - Veneroni, Silvia
AU - Daidone, Maria Grazia
AU - Gariboldi, Manuela
AU - Pierotti, Marco A.
PY - 2005/6
Y1 - 2005/6
N2 - Data from microarray studies have been used to develop predictive models for treatment outcome in breast cancer, such as a recently proposed predictive model for antiestrogen response after tamoxifen treatment that was based on the expression ratio of two genes. We attempted to validate this model on an independent cohort of 58 patients with resectable estrogen receptor-positive breast cancer. We measured expression of the genes HOXB13 and IL17BR with real time-quantitative polymerase chain reaction and assessed the association between their expression and outcome by use of univariate logistic regression, area under the receiver-operating-characteristic curve (AUC), a two-sample t test, and a Mann-Whitney test. We also applied standard supervised methods to the original microarray dataset and to another independent dataset from similar patients to estimate the classification accuracy obtainable by using more than two genes in a microarray-based predictive model. We could not validate the performance of the two-gene predictor on our cohort of samples (relation between outcome and the following genes estimated by logistic regression: for HOXB13, odds ratio [OR] = 1.04, 95% confidence interval [CI] = 0.92 to 1.16, P = .54; for IL17BR, OR = 0.69, 95% CI = 0.40 to 1.20, P = .18; and for HOXB13/IL17BR, OR = 1.30, 95% CI = 0.88 to 1.93, P = .18). Similar results were obtained with the AUC, a two-sample two-sided t test, and a Mann-Whitney test. In addition, estimates of classification accuracies applied to two independent microarray datasets highlighted the poor performance of treatment-response predictive models that can be achieved with the sample sizes of patients and informative genes to date.
AB - Data from microarray studies have been used to develop predictive models for treatment outcome in breast cancer, such as a recently proposed predictive model for antiestrogen response after tamoxifen treatment that was based on the expression ratio of two genes. We attempted to validate this model on an independent cohort of 58 patients with resectable estrogen receptor-positive breast cancer. We measured expression of the genes HOXB13 and IL17BR with real time-quantitative polymerase chain reaction and assessed the association between their expression and outcome by use of univariate logistic regression, area under the receiver-operating-characteristic curve (AUC), a two-sample t test, and a Mann-Whitney test. We also applied standard supervised methods to the original microarray dataset and to another independent dataset from similar patients to estimate the classification accuracy obtainable by using more than two genes in a microarray-based predictive model. We could not validate the performance of the two-gene predictor on our cohort of samples (relation between outcome and the following genes estimated by logistic regression: for HOXB13, odds ratio [OR] = 1.04, 95% confidence interval [CI] = 0.92 to 1.16, P = .54; for IL17BR, OR = 0.69, 95% CI = 0.40 to 1.20, P = .18; and for HOXB13/IL17BR, OR = 1.30, 95% CI = 0.88 to 1.93, P = .18). Similar results were obtained with the AUC, a two-sample two-sided t test, and a Mann-Whitney test. In addition, estimates of classification accuracies applied to two independent microarray datasets highlighted the poor performance of treatment-response predictive models that can be achieved with the sample sizes of patients and informative genes to date.
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U2 - 10.1093/jnci/dji153
DO - 10.1093/jnci/dji153
M3 - Article
C2 - 15956654
AN - SCOPUS:21444453976
VL - 97
SP - 927
EP - 930
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 12
ER -