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A prognostic gene expression profile that predicts circulating tumor cell presence in breast cancer patients.

Molloy TJ, Roepman P, Naume B, van't Veer LJ - PLoS ONE (2012)

Bottom Line: The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer.In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome.This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

ABSTRACT
The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer. Meta-analyses of several established prognostic breast cancer gene expression profiles in large patient cohorts have demonstrated that despite sharing few genes, their delineation of patients into "good prognosis" or "poor prognosis" are frequently very highly correlated, and combining prognostic profiles does not increase prognostic power. In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome. Microarray gene expression data from an initial training cohort of 72 breast cancer patients for which CTC status had been determined in a previous study using a multimarker QPCR-based assay was used to develop a CTC-predictive profile. The generated profile was validated in two independent datasets of 49 and 123 patients and confirmed to be both predictive of CTC status, and independently prognostic. Importantly, the "CTC profile" also provided prognostic information independent of the well-established and powerful '70-gene' prognostic breast cancer signature. This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays.

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Kaplan-Meier survival analysis of a second independent validation patient cohort consisting of 123 early-stage breast cancer patients from the van de Vijver [8], [18] dataset classified with the CTC-profile (A), MammaPrint 70-gene profile (B), and both classifications combined (C).
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pone-0032426-g003: Kaplan-Meier survival analysis of a second independent validation patient cohort consisting of 123 early-stage breast cancer patients from the van de Vijver [8], [18] dataset classified with the CTC-profile (A), MammaPrint 70-gene profile (B), and both classifications combined (C).

Mentions: Further independent validation of the prognostic power of the CTC-profile was performed using publically-available microarray data from the primary tumors of 123 early-stage lymph-node negative breast cancer patients [8]. CTC-profile classification was determined using 33 of the 34 profile genes present on the array platform. Classification by the CTC-profile showed a HR of 3.16 (p = 0.006), confirming the prognostic value of the identified gene set. Patients with a CTC-negative profile had a 5-year disease-free survival (DFS) of 88% and a 10-year DFS of 83% versus 65% and 53%, respectively, for patients with a CTC-positive profile (Figure 3A). For comparison, the partial 22-gene CTC profile was also validated in this dataset. The correlation in classification to the 33-gene CTC profile was again high (r2 = 0.968), though it had somewhat lower prognostic value (HR = 2.56, p = 0.018).


A prognostic gene expression profile that predicts circulating tumor cell presence in breast cancer patients.

Molloy TJ, Roepman P, Naume B, van't Veer LJ - PLoS ONE (2012)

Kaplan-Meier survival analysis of a second independent validation patient cohort consisting of 123 early-stage breast cancer patients from the van de Vijver [8], [18] dataset classified with the CTC-profile (A), MammaPrint 70-gene profile (B), and both classifications combined (C).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285692&req=5

pone-0032426-g003: Kaplan-Meier survival analysis of a second independent validation patient cohort consisting of 123 early-stage breast cancer patients from the van de Vijver [8], [18] dataset classified with the CTC-profile (A), MammaPrint 70-gene profile (B), and both classifications combined (C).
Mentions: Further independent validation of the prognostic power of the CTC-profile was performed using publically-available microarray data from the primary tumors of 123 early-stage lymph-node negative breast cancer patients [8]. CTC-profile classification was determined using 33 of the 34 profile genes present on the array platform. Classification by the CTC-profile showed a HR of 3.16 (p = 0.006), confirming the prognostic value of the identified gene set. Patients with a CTC-negative profile had a 5-year disease-free survival (DFS) of 88% and a 10-year DFS of 83% versus 65% and 53%, respectively, for patients with a CTC-positive profile (Figure 3A). For comparison, the partial 22-gene CTC profile was also validated in this dataset. The correlation in classification to the 33-gene CTC profile was again high (r2 = 0.968), though it had somewhat lower prognostic value (HR = 2.56, p = 0.018).

Bottom Line: The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer.In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome.This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

ABSTRACT
The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer. Meta-analyses of several established prognostic breast cancer gene expression profiles in large patient cohorts have demonstrated that despite sharing few genes, their delineation of patients into "good prognosis" or "poor prognosis" are frequently very highly correlated, and combining prognostic profiles does not increase prognostic power. In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome. Microarray gene expression data from an initial training cohort of 72 breast cancer patients for which CTC status had been determined in a previous study using a multimarker QPCR-based assay was used to develop a CTC-predictive profile. The generated profile was validated in two independent datasets of 49 and 123 patients and confirmed to be both predictive of CTC status, and independently prognostic. Importantly, the "CTC profile" also provided prognostic information independent of the well-established and powerful '70-gene' prognostic breast cancer signature. This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays.

Show MeSH
Related in: MedlinePlus