Comparison of the Predictive Accuracy of DNA Array-Based Multigene Classifiers across cDNA Arrays and Affymetrix GeneChips

Stec, James; Wang, Jing; Coombes, Kevin R.; Ayers, Mark; Hoersch, Sebastian; Gold, David; Ross, Jeffrey S.; Hess, Kenneth R.; Tirrell, Stephen; Linette, Gerald P.; Hortobágyi, Gabriel N.; Symmans, W. Fraser; Pusztai, Lajos

doi:10.1016/s1525-1578(10)60565-x

Cited by 48 publications

(38 citation statements)

References 17 publications

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“…A subset of patients (n ϭ 33) included in the current study was also included in a separate analysis when RNA was profiled on a cDNA microarray (8). Tau was not part of the final cDNA result-based predictor; however, it was among the top differentially expressed genes (20). Low tau mRNA expression was significantly more common among cases with pCR compared with those with residual disease.…”

Section: Discussionmentioning

confidence: 99%

Microtubule-associated protein tau: A marker of paclitaxel sensitivity in breast cancer

Rouzier

Rajan

Wagner

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Breast cancers show variable sensitivity to paclitaxel. There is no diagnostic test to identify tumors that are sensitive to this drug. We used U133A chips to identify genes that are associated with pathologic complete response (pCR) to preoperative paclitaxelcontaining chemotherapy in stage I-III breast cancer (n ‫؍‬ 82). Tau was the most differentially expressed gene. Tumors with pCR had significantly lower (P < 0.3 ؋ 10 ؊5 ) mRNA expression. Tissue arrays from 122 independent but similarly treated patients were used for validation by immunohistochemistry. Seventy-four percent of pCR cases were tau protein negative; the odds ratio for pCR was 3.7 (95% confidence interval, 1.6 -8.6; P ϭ 0.0013). In multivariate analysis, nuclear grade (P < 0.01), age <50 (P ϭ 0.03), and taunegative status (P ϭ 0.04) were independent predictors of pCR. Small interfering RNA experiments were performed to examine whether down-regulation of tau increases sensitivity to chemotherapy in vitro. Down-regulation of tau increased sensitivity of breast cancer cells to paclitaxel but not to epirubicin. Tubulin polymerization assay was used to assess whether tau modulates binding of paclitaxel to tubulin. Preincubation of tubulin with tau resulted in decreased paclitaxel binding and reduced paclitaxelinduced microtubule polymerization. These data suggest that low tau expression renders microtubules more vulnerable to paclitaxel and makes breast cancer cells hypersensitive to this drug. Low tau expression may be used as a marker to select patients for paclitaxel therapy. Inhibition of tau function might be exploited as a therapeutic strategy to increase sensitivity to paclitaxel. adjuvant therapy ͉ drug resistance

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Section: Discussionmentioning

confidence: 99%

Microtubule-associated protein tau: A marker of paclitaxel sensitivity in breast cancer

Rouzier

Rajan

Wagner

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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380

301

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“…Of the 82 RNA specimens used in this analysis, 33 were included in a previous pharmacogenomic analysis using cDNA arrays (6). These 33 cases were profiled on both platforms (Affymetrix U133A and proprietary cDNA) and the results of the cross platform comparison of gene expression data were published separately (7). All patients underwent surgery after completion of 24 weeks of preoperative chemotherapy.…”

Section: Methodsmentioning

confidence: 99%

Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy

Rouzier

Perou

Symmans³

et al. 2005

Clinical Cancer Research

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Purpose: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. Experimental Design: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported ''breast intrinsic''gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. Results: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor^negative subtypes. Conclusions: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel-and doxorubicin-containing preoperative chemotherapy than the luminal and normallike cancers.Breast cancer is a clinically heterogeneous disease. Histologically similar tumors may have different prognoses and may respond to therapy differently. It is believed that these differences in clinical behavior are due to molecular differences between histologically similar tumors. DNA microarray technology is ideally suited to reveal such molecular differences. A novel molecular classification of breast cancer based on gene expression profiles was recently proposed (1). The investigators identified a set of stably expressed genes (''intrinsic gene set''; n = 534) that accounted for much of the molecular differences between 42 breast cancers and did hierarchical cluster analysis to identify subgroups of cancers with separate gene expression profiles. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses (1 -4). These results were confirmed in follow-up experiments by the same group and others using larger numbers of cases. The basal-like (mostly estrogen receptor negative) and erbB2+ (mostly HER-2 amplified and estrogen receptor negative) subgroups had the shortest relapse-free and overall survival, whereas the luminal-type (estrogen receptorpositive) tumors had a more favorable clinical outcome (2 -4).

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“…Thirty-three of the 97 RNA specimens were included in a previous pharmacogenomic analysis using cDNA arrays (6). These 33 cases were profiled on both platforms (Affymetrix U133A and proprietary cDNA), and the results of the cross-platform comparison of gene expression data were published separately (8).…”

Section: Methodsmentioning

confidence: 99%

Reproducibility of Gene Expression Signature–Based Predictions in Replicate Experiments

Anderson

Hess

Kapoor

et al. 2006

Clinical Cancer Research

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Purpose: The goals of this analysis were to (a) determine concordance of gene expression results from replicate experiments, (b) examine prediction agreement of multigene predictors on replicate data, and (c) assess the robustness of prediction results in the face of noise. Patients and Methods: Affymetrix U133A gene chips were used for gene expression profiling of 97 fine-needle aspiration biopsies from breast cancer. Thirty-five cases were profiled in replicates: 17 within the same laboratory, 11 in two different laboratories, and 15 to assess manual and robotic labeling. We used data from 62 cases to develop 111 distinct pharmacogenomic predictors of response to therapy. These were tested on cases profiled in duplicates to determine prediction agreement and accuracy. To evaluate the robustness of the pharmacogenomic predictors, we also introduced random noise into the informative genes in one half of the replicates.

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Comparison of the Predictive Accuracy of DNA Array-Based Multigene Classifiers across cDNA Arrays and Affymetrix GeneChips

Cited by 48 publications

References 17 publications

Microtubule-associated protein tau: A marker of paclitaxel sensitivity in breast cancer

Microtubule-associated protein tau: A marker of paclitaxel sensitivity in breast cancer

Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy

Reproducibility of Gene Expression Signature–Based Predictions in Replicate Experiments

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