Nav: Home

New standard helps ensure accurate clinical measurements of HER2 breast cancer gene

August 17, 2016

A new measurement standard developed by the National Institute of Standards of Technology (NIST) has been used successfully by the Frederick National Laboratory for Cancer Research to check the performance of next-generation DNA-sequencing technologies for evaluating gene variations associated with an increased risk of breast cancer.

Scientists at the Molecular Characterization Laboratory (MCL) at the Frederick National Lab, which is sponsored by the National Cancer Institute, evaluated the usefulness of the NIST HER2 Standard Reference Material (SRM 2373) for ensuring the accuracy of measurements of HER2 gene copy numbers. Excessive copies of the HER2 gene indicate heightened risk for an aggressive form of breast cancer.

The trial run "clearly demonstrated the value of SRM 2373" for both evaluating assay performance and "increasing confidence in reporting HER2 amplification for clinical applications," Frederick National Lab and NIST researchers report in the new issue of the Journal of Molecular Diagnostics.

"The gene is a biomarker for treatment selection. Diagnostic sequencing tests like HER2 assays make it possible to select the best treatment for individual patients based on the genetic makeup of their tumors," said MCL Director Mickey Williams.

Normal cells have two copies of HER2, but about 20 to 25 percent of breast cancers have multiple copies of the gene, resulting in overproduction of the HER2-encoded protein. This gene amplification stimulates tumors to be particularly fast growing in this subset of breast cancer patients--about 40,000 women in the United States annually.

Fortunately, these patients can be treated with a monoclonal antibody called trastuzumab (brand name Herceptin) that targets and inhibits the growth of tumor cells with higher-than-normal levels of the HER2 protein. The combination of more traditional chemotherapy drugs plus trastuzumab has been found to increase long-term survival rates significantly.

The treatment also can have adverse side effects, so it's important to screen for those patients who would benefit from it by testing them. However, the two primary tests used prior to the ongoing transition to genomic screening--one relying on fluorescent probes and the other on tissue staining--have been prone to error. An estimated 20 percent of tests were estimated to yield inaccurate results, either false positives or false negatives.

In fact, NIST had originally set out to develop measurement tools to improve the accuracy of those diagnostic tests. But with the rapid emergence of next-generation genome sequencing, NIST chose, instead, to focus on developing measurement references that support the more sensitive and more specific detection capabilities of the new technologies.

SRM 2373 consists of DNA extracted from five breast-cancer cell lines, each with a different average number of copies of the HER2 genes, relative to a selected set of unvarying reference genes. Across the five-vial set, NIST-certified ratios of HER2 copies to the reference genes range from just over one to about 18.

"The collaboration with the Frederick National Lab is very valuable for NIST to ensure that the reference materials we develop are relevant and timely to meet the needs of the clinical and research communities in the rapidly changing field of molecular diagnosis of cancer," said NIST biochemist Kenneth Cole.

The HER2 reference material is the latest addition to a growing list of measurement tools that NIST has developed to help advance genomics-inspired precision medicine. NIST also is working with Frederick National Lab researchers and industry to improve detection and reliable measurement of cell-free circulating tumor DNA, sometimes called liquid biopsies. Circulating tumor DNA has been detected in many cancers and might be used to monitor patients' therapeutic progress and whether tumors mutate to become resistant to treatments.

NIST recently signed a three-year Cooperative Research and Development Agreement with SeraCare Life Sciences to collaborate on an interlaboratory study comparing measurements of the company's circulating tumor DNA reference material.

In 2015, NIST and its partners in the Genome in a Bottle Consortium issued NIST Reference Material (RM) 8398 Human DNA for Whole-Genome Variant Assessment, for which about 77 percent of the genome is characterized with high levels of confidence. The Food and Drug Administration used the genome reference material as its "truth set" for its just-completed PrecisionFDA Consistency Challenge, intended to advance quality standards for whole human genome sequencing.

In May 2016, NIST issued a "Peptide Mixture for Proteomics" (RM 8321), which contains 440 synthetic peptides, or segments of proteins. Proteomics is the identification and study of proteins, which are encoded by genes and are, ultimately, the body's "doers," acting alone or in groups to drive processes involved in health and disease.
-end-
Articles:

H-J. He, J. Almeida, S. Lund, C.R. Steffen, S. Choquette and K.D. Cole. 2016. Development of NIST Standard Reference Material 2373: Genomic DNA Standards for HER2 Measurements. Biomolecular Detection and Quantification, Published June 2016. DOI: doi:10.1016/j.bdq.2016.02.001

C-J. Lih, H. Si, B. Das, R.D. Harrington, K.N. Harper, D.J. Sims, P.M. McGregor, C.E. Camalier, A.Y. Kayserian, P.M. Williams, H-J He, J. Almeida, S.L. Lund, S. Choquette and K.D. Cole. Certified DNA Reference Materials to Compare HER2 Gene Amplification Measurements Using Next-Generation Sequencing Methods. Journal of Molecular Diagnostics. Available online July 25, 2016. DOI: 10.1016/j.jmoldx.2016.05.008

National Institute of Standards and Technology (NIST)

Related Breast Cancer Articles:

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.
Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.
More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.
Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.
Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.
More Breast Cancer News and Breast Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...