Skip to main content

EGAPP Issues Cancer Genetic Test Recommendations

This article has been updated to clarify that EGAPP is an independent entity that was formed by CDC, rather than an arm of the CDC.

NEW YORK (GenomeWeb News) — The independent Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (EWG) has released a cautious set of recommendations about the validity and utility of three genetic tests or methods that are aimed at healthcare providers, public health practitioners, policy makers, and consumers.

EGAPP is an initiative that was established by the Office of Public Health Genomics at the US Centers for Disease Control and Prevention.

After conducting an evidence-based analysis, EWG said it could recommend offering genetic testing for Lynch syndrome to newly diagnosed colorectal cancer patients, but that it did not find enough evidence to recommend for or against two other types of genetic tests, for breast cancer and metastatic colorectal cancer. The effectiveness of these tests was studied for analytical validity, clinical validity, and clinical utility.

The CDC on Friday released three new papers, which evaluated tests for Lynch syndrome for use in colorectal cancer cases, for using tumor gene expression profiles for certain breast cancer patients, and for the routine use of UGT1A1 genotyping in patients with metastatic colorectal cancer.

EWG found sufficient evidence to recommend genetic tests for Lynch syndrome to individuals with newly diagnosed colorectal cancer to reduce morbidity and mortality in relatives, but the group found insufficient evidence to recommend a specific genetic testing strategy among those the group examined.

The group constructed a chain of evidence linking the genetic testing for Lynch syndrome with improved health outcomes in their relatives. EWG concluded that there is "moderate certainty that such a strategy would provide moderate population benefit."

EWG said it did not find evidence to recommend for or against using tumor gene expression profiles to improve outcomes in defined groups of women with breast cancer. While the group found preliminary evidence of potential benefit to some women facing certain treatment options, it could not rule out the potential harm for others. Those findings left the group with insufficient evidence to assess the benefits versus the harms of the proposed uses of the tests, said the group.

Some performance data were available for MammaPrint, which is made by Agendia, and Genomic Health's Oncotype DX test, although estimates about sensitivity and specificity could not be made. For Oncotype DX, the EWG found "adequate evidence" regarding disease recurrence and response to chemotherapy.

The working group also found "adequate evidence" to characterize the association of MammaPrint with future metastases, but inadequate evidence to assess the added value to standard risk stratification, and it could not determine the best population for the test.

The EWG found no evidence regarding the clinical utility of MammaPrint and Quest Diagnostics' H:I test, and "inadequate evidence" for Oncotype DX.

"These technologies have potential for both benefit and harm," the group said, adding that there is a need for "further development and evaluation."

EWG also did not find enough evidence to recommend for or against the routine use of UGT1A1 genotyping as way of avoiding adverse reactions to the drug irinotecan for patients with metastatic colorectal cancer.

The group found no intervention trials showing that targeted dosing of the drug based on UGT1A1 genotyping could reduce the rates of two specific adverse events, severe neutropenia or diarrhea.

Although observational studies have found "a significant association" between certain genotypes and the occurrence of severe neutropenia and a possible, but not statistically significant, association with severe diarrhea, the group also found that reducing the drug's dosage could result in reducing effectiveness of the treatment, and may harm the patients. Likewise, a higher dosage of the drug could be warranted among individuals who are at lower risk of adverse drug events.

The preliminary models suggest that "even if targeted dosing were to be highly effective, it is not clear that benefits (reduced drug events) outweigh harms (unresponsive tumors)."

The recommendations are published in the current issue of Genetics in Medicine.

Filed under

The Scan

US Supports Patent Waivers

NPR reports that the Biden Administration has announced its support for waiving intellectual property protections for SARS-CoV-2 vaccines.

Vaccines Versus Variants

Two studies find the Pfizer-BioNTech SARS-CoV-2 vaccine to be effective against viral variants, and Moderna reports on booster shots to combat variants.

CRISPR for What Ails You

The Wall Street Journal writes that CRISPR-based therapies could someday be used to treat common conditions like heart attacks.

Nature Papers Review Integration of Single-Cell Assay Data, Present Approach to Detect Rare Variants

In Nature this week: review of ways to integrate data from single-cell assays, and more.