Clinical utility of gene-expression profiling in women with early breast cancer: an overview of systematic reviews

Abstract

Purpose This overview systematically evaluates the clinical utility of using Oncotype DX and MammaPrint gene-expression profiling tests to direct treatment decisions in women with breast cancer. The findings are intended to inform an updated recommendation from the Evaluation of Genomic Applications in Practice and Prevention Working Group. Methods Evidence reported in systematic reviews evaluating the clinical utility of Oncotype DX and MammaPrint, as well as the ability to predict treatment outcomes, change in treatment decisions, and cost-effectiveness, was qualitatively synthesized. Results Five systematic reviews found no direct evidence of clinical utility for either test. Indirect evidence showed Oncotype DX was able to predict treatment effects of adjuvant chemotherapy, whereas no evidence of predictive value was found for MammaPrint. Both tests influenced a change in treatment recommendations in 21 to 74% of participants. The cost-effectiveness of Oncotype DX varied with the alternative compared. For MammaPrint, lack of evidence of the predictive value led to uncertainty in the cost-effectiveness. Conclusion No studies were identified that provided direct evidence that using gene-expression profiling tests to direct treatment decisions improved outcomes in women with breast cancer. Three ongoing studies may provide direct evidence for determining the clinical utility of gene-expression profiling testing.

Recommendations from the EGAPP Working Group: does the use of Oncotype DX tumor gene expression profiling to guide treatment decisions improve outcomes in patients with breast cancer?

“…EWG members reviewed the original evidence report and recommendation statement, an overview of systematic reviews on clinical utility and cost-effectiveness of gene expression profiling published between 2009 and 2013, 21 key primary publications, and other sources of information. The final EWG recommendation statement was based on magnitude of effect, certainty of evidence, and consideration of contextual factors (by a process outlined in Table 6 …”

“…[16][17][18][19]21 Results from six of these studies indicate that 13-34% fewer patients overall were recommended for chemotherapy after use of Oncotype DX testing. 21 • The quality of evidence from these studies was assessed as low by GRADE criteria because the studies were highly heterogeneous with respect to patient populations and the criteria used to make initial treatment decisions.…”

“…32 • When evaluated by the GRADE criteria, the quality of evidence indicating that Oncotype DX RS has clinical utility was assessed as very low. 21 Low quality was not due to conflicting studies or studies demonstrating lack of benefit. Instead, it reflected important limitations in Table 2 Selected findings on the ability of Oncotype DX RS to predict benefit from adjuvant chemotherapy Relative risks and hazard ratios compare the risk of recurrence (or death) for a given recurrence score group with or without chemotherapy.…”

“…15 Since the publication of the evidence review and EGAPP recommendation statement, several systematic reviews have been published addressing questions relating to the clinical utility and cost-effectiveness of Oncotype DX and MammaPrint. [16][17][18][19][20] On the basis of an overview of the findings of five of these systematic reviews 21 and additional published evidence, the EWG decided to prepare an updated version of its 2009 recommendation statement. This update focuses on the Oncotype DX test.…”

Non-homologous end-joining protein expression screen from radiosensitive cancer patients yields a novel DNA double strand break repair phenotype

“…This is a significant impediment to personalization of radiotherapy, used in over 50% of cancer patients (2). Once more 'radiosensitivity genes' are known, pre-therapy predictive testing could be envisaged, along the lines of gene expression tests used in cancer management (3).…”