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Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer

Hess, Kenneth R., Anderson, Keith, Symmans, W. Fraser, Valero, Vicente, Ibrahim, Nuhad, Mejia, Jaime A., Booser, Daniel, Theriault, Richard L., Buzdar, Aman U., Dempsey, Peter J., Rouzier, Roman, Sneige, Nour, Ross, Jeffrey S., Vidaurre, Tatiana, Gómez, Henry L., Hortobagyi, Gabriel N., Pusztai, Lajos·2006·Journal of Clinical Oncology

Abstract

Purpose: We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases. Patients and Methods: One hundred thirty-three patients with stage I-III breast cancer were included. Pretreatment gene expression profiling was performed with oligonecleotide microarrays on fine-needle aspiration specimens. We developed predictors of pCR from 82 cases and assessed accuracy on 51 independent cases. Results: Overall pCR rate was 26% in both cohorts. In the training set, 56 probes were identified as differentially expressed between pCR versus residual disease, at a false discovery rate of 1%. We examined the performance of 780 distinct classifiers (set of genes + prediction algorithm) in full cross-validation. Many predictors performed equally well. A nominally best 30-probe set Diagonal Linear Discriminant Analysis classifier was selected for independent validation. It showed significantly higher sensitivity (92% v 61%) than a clinical predictor including age, grade, and estrogen receptor status. The negative predictive value (96% v 86%) and area under the curve (0.877 v 0.811) were nominally better but not statistically significant. The combination of genomic and clinical information yielded a predictor not significantly different from the genomic predictor alone. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant. Conclusion: A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients).

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Metadata

Authors
Hess, K. R., Anderson, K., Symmans, W. F., Valero, V., Ibrahim, N., Mejia, J. A., Booser, D., Theriault, R. L., Buzdar, A. U., Dempsey, P. J., Rouzier, R., Sneige, N., Ross, J. S., Vidaurre, T., Gómez, H. L., Hortobagyi, G. N., & Pusztai, L.
Venue
Journal of Clinical Oncology
Published
2006-09-10
Volume
24
Issue
26
Pages
4236-4244
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
OpenAlex
W2154899482
Cited by
721
References
26
FWCI
23.34
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer. https://app.cochat.ai/papers/10.1200/jco.2006.05.6861
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Hess, K. R., Anderson, K., Symmans, W. F., Valero, V., Ibrahim, N., Mejia, J. A., Booser, D., Theriault, R. L., Buzdar, A. U., Dempsey, P. J., Rouzier, R., Sneige, N., Ross, J. S., Vidaurre, T., Gómez, H. L., Hortobagyi, G. N., & Pusztai, L. (2006). Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2006.05.6861

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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