Prospective comparison of clinical and genomic multivariate predictors of response to neoadjuvant chemotherapy in breast cancer - PubMed (original) (raw)

Comparative Study

Prospective comparison of clinical and genomic multivariate predictors of response to neoadjuvant chemotherapy in breast cancer

Jae K Lee et al. Clin Cancer Res. 2010.

Abstract

Purpose: Several different multivariate prediction models using routine clinical variables or multigene signatures have been proposed to predict pathologic complete response to combination chemotherapy in breast cancer. Our goal was to compare the performance of four conceptually different predictors in an independent cohort of patients.

Experimental design: Gene expression profiling was done on fine-needle aspirations of 100 stage I to III breast cancers before preoperative paclitaxel, 5-fluorouracil, doxorubicin, and cyclophosphamide combination chemotherapy. Pathologic response was correlated with prediction results from a clinical nomogram, a human cancer-derived genomic predictor (DLDA30), a cell line-based genomic predictor [in vitro coexpression extrapolation (COXEN)], and an optimized cell line-derived (in vivo COXEN) predictor. None of the 100 test cases were used in the development of these predictors.

Results: The in vitro COXEN using a combination of four individual drug sensitivity predictions derived from cell lines was not predictive [area under the receiver operator characteristic curve (AUC), 0.5; 95% confidence interval, (95% CI), 0.41-0.59]. The clinical nomogram (AUC, 0.73; 95% CI, 0.65-0.80) and the DLDA30 (AUC, 0.73; 95% CI, 0.66-0.80) genomic predictor had similar performances. The in vivo COXEN that used informative genes from cell lines but was trained on a separate human data set also showed significant predictive value (AUC, 0.67; 95% CI, 0.60-0.74). These three different prediction scores correlated with each other and were significant in univariate but not in multivariate analysis.

Conclusions: Three conceptually different predictors performed similarly in this validation study and tended to identify the same patients as responders. A genomic predictor that relied solely on a composite of individual drug sensitivity predictions from cell lines did not show any predictive value.

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Conflict of interest statement

Conflicts of interest

The authors declared no conflicts of interest.

Figures

Figure 1

Figure 1. Receiver Operating Characteristics (ROC) curve analysis of the four conceptually different chemotherapy response predictors

ROC curves are shown for the clinical nomogram, the DLDA30 predictor, the in vitro combined T/FAC COXEN GEM and the in vivo combined T/FAC COXEN GEM.

Figure 2

Figure 2. Correlation between ranks of prediction scores

Ranks of predicted scores of the in vivo-GEM, DLDA30 predictor and clinical nomogram were plotted against each other. Rank-based Spearman correlation and p-value were calculated for each pair of comparisons.

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