Tumor Gene Expression Profiling in Women with Breast Cancer Test Category : Prognostic

Differences in the expression of specific genes within breast tumors have been associated with risk of recurrence after treatment. Most women with Stage I or II node-negative breast cancer (especially when estrogen-receptor positive and treated with tamoxifen) remain disease-free at 10 years. Information on risk of recurrence could help identify women most likely to benefit from chemotherapy. Several clinically available gene expression profiles (GEP) provide “recurrence risk scores” that are intended to supplement information used by clinicians and patients in treatment decision-making.

recommendation for or against the use of tumor gene expression profiles to improve outcomes in defined populations of women with breast cancer."[1] Guidelines by professional groups National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology -Breast Cancer [12] American Society of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer [13] ECRI Institute: Policy Statement [14] American Society of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer [13] ECRI Institute: Policy Statement [14] * independent groups include the US Preventive Services Task Force (USPSTF) and Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group.

Evidence Overview
Analytic Validity : Test accuracy and reliability in measuring differences in expression of relevant genes (analytic sensitivity and specificity).
A 2009 EGAPP Working Group recommendation statement [1]suggested that: limited published data are available regarding assay performance of clinically available GEP, analytic sensitivity and specificity cannot be estimated because no reference technology ("gold standard") is available for comparison, initial test failure rates ranged from 12-19%, partly because of problems with tissue sampling and processing.
One published reference on Oncotype DX analytical validity sponsored by the test manufacturer is available.[15] he FDA summary of MammaPrint provided information on result and classification accuracy [16] Clinical Validity : Test accuracy and reliability in predicting breast cancer recurrence and benefit from chemotherapy (predictive value).
Several studies have reported on the clinical validity for Oncotype DX. [17][18][19] [20] A recent study reported an association between the Oncotype DX recurrence score and risk of locoregional recurrence using data from the NSABP B-14 and B-20 trials.[21] Published studies regarding MammaPrint have suggested a significant association between the MammaPrint Index (high vs. low risk) and 5 and 10 year distant recurrence rates.[22][23] [24]However: efficacy in ER positive vs. negative cases is unclear, [1] added value beyond standard risk stratification is unclear.[1] A parallel, prospective evaluation was recently published comparing three gene expression profile tests analogous to Oncotype DX, Mammaprint and the H:I Ratio Test.
All were significantly associated with time to progression; however, concordance of results among the three classifiers was relatively low, classifying only 45-61% of patients in the same category.[25] Clinical Utility: Net benefit of test in improving health outcomes.
Retrospective analysis of one arm of a single prospective trial (NSABP B-20) showed that chemotherapy (in addition to tamoxifen) was most beneficial in women in the Oncotype DX high risk category.[20] A prospective multicenter study published in 2010 reported on the impact of Oncotype DX on patient and physician adjuvant chemotherapy decisions.[9] Analyses of economic implications of Oncotype DX have been published.[5][26] 2010 publication explored women's experiences with genomic testing for breast cancer recurrence risk in terms of how scores were received and understood.[27] A 2009 EGAPP recommendation reported that no direct evidence linked the use of MammaPrint or the H:I test to clinical outcomes.[1] Ongoing trials include: TAILORx trial (Oncotype DX) [28] recommendation for or against the use of tumor gene expression profiles to improve outcomes in defined populations of women with breast cancer."[1] Guidelines by professional groups National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology -Breast Cancer [12] American Society of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer [13] ECRI Institute: Policy Statement [14] American Society of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer [13] ECRI Institute: Policy Statement [14] * independent groups include the US Preventive Services Task Force (USPSTF) and Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group.

Evidence Overview
Analytic Validity : Test accuracy and reliability in measuring differences in expression of relevant genes (analytic sensitivity and specificity).
A 2009 EGAPP Working Group recommendation statement [1]suggested that: limited published data are available regarding assay performance of clinically available GEP, analytic sensitivity and specificity cannot be estimated because no reference technology ("gold standard") is available for comparison, initial test failure rates ranged from 12-19%, partly because of problems with tissue sampling and processing.
One published reference on Oncotype DX analytical validity sponsored by the test manufacturer is available.[15] he FDA summary of MammaPrint provided information on result and classification accuracy [16] Clinical Validity : Test accuracy and reliability in predicting breast cancer recurrence and benefit from chemotherapy (predictive value).

Several studies have reported on the clinical validity for Oncotype DX.[17][18][19][20]
A recent study reported an association between the Oncotype DX recurrence score and risk of locoregional recurrence using data from the NSABP B-14 and B-20 trials.[21] Published studies regarding MammaPrint have suggested a significant association between the MammaPrint Index (high vs. low risk) and 5 and 10 year distant recurrence rates.[22][23] [24]However: efficacy in ER positive vs. negative cases is unclear, [1] added value beyond standard risk stratification is unclear.[1] A parallel, prospective evaluation was recently published comparing three gene expression profile tests analogous to Oncotype DX, Mammaprint and the H:I Ratio Test.
All were significantly associated with time to progression; however, concordance of results among the three classifiers was relatively low, classifying only 45-61% of patients in the same category.[25] Clinical Utility: Net benefit of test in improving health outcomes.
Retrospective analysis of one arm of a single prospective trial (NSABP B-20) showed that chemotherapy (in addition to tamoxifen) was most beneficial in women in the Oncotype DX high risk category.[20] A prospective multicenter study published in 2010 reported on the impact of Oncotype DX on patient and physician adjuvant chemotherapy decisions.[9] Analyses of economic implications of Oncotype DX have been published.[5][26] 2010 publication explored women's experiences with genomic testing for breast cancer recurrence risk in terms of how scores were received and understood.[27] A 2009 EGAPP recommendation reported that no direct evidence linked the use of MammaPrint or the H:I test to clinical outcomes.[1] Ongoing trials include: TAILORx trial (Oncotype DX) [28] recommendation for or against the use of tumor gene expression profiles to improve outcomes in defined populations of women with breast cancer."[1] Guidelines by professional groups National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology -Breast Cancer [12] American Society of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer [13] ECRI Institute: Policy Statement [14] American Society of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer [13] ECRI Institute: Policy Statement [14] * independent groups include the US Preventive Services Task Force (USPSTF) and Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group.

Evidence Overview
Analytic Validity : Test accuracy and reliability in measuring differences in expression of relevant genes (analytic sensitivity and specificity).
A 2009 EGAPP Working Group recommendation statement [1]suggested that: limited published data are available regarding assay performance of clinically available GEP, analytic sensitivity and specificity cannot be estimated because no reference technology ("gold standard") is available for comparison, initial test failure rates ranged from 12-19%, partly because of problems with tissue sampling and processing.
One published reference on Oncotype DX analytical validity sponsored by the test manufacturer is available.[15] he FDA summary of MammaPrint provided information on result and classification accuracy [16] Clinical Validity : Test accuracy and reliability in predicting breast cancer recurrence and benefit from chemotherapy (predictive value).

Several studies have reported on the clinical validity for Oncotype DX.[17][18][19][20]
A recent study reported an association between the Oncotype DX recurrence score and risk of locoregional recurrence using data from the NSABP B-14 and B-20 trials.[21] Published studies regarding MammaPrint have suggested a significant association between the MammaPrint Index (high vs. low risk) and 5 and 10 year distant recurrence rates.[22][23][24]However: efficacy in ER positive vs. negative cases is unclear, [1] added value beyond standard risk stratification is unclear.[1] A parallel, prospective evaluation was recently published comparing three gene expression profile tests analogous to Oncotype DX, Mammaprint and the H:I Ratio Test.
All were significantly associated with time to progression; however, concordance of results among the three classifiers was relatively low, classifying only 45-61% of patients in the same category.[25] Clinical Utility: Net benefit of test in improving health outcomes.
Retrospective analysis of one arm of a single prospective trial (NSABP B-20) showed that chemotherapy (in addition to tamoxifen) was most beneficial in women in the Oncotype DX high risk category.[20] A prospective multicenter study published in 2010 reported on the impact of Oncotype DX on patient and physician adjuvant chemotherapy decisions.[9] Analyses of economic implications of Oncotype DX have been published.[5][26] 2010 publication explored women's experiences with genomic testing for breast cancer recurrence risk in terms of how scores were received and understood.[27] A 2009 EGAPP recommendation reported that no direct evidence linked the use of MammaPrint or the H:I test to clinical outcomes.[1] Ongoing trials include: TAILORx trial (Oncotype DX) [28]