Practice Guidelines Released for HER2 Testing in Breast Cancer

January 1, 2007

The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) have published a clinical practice guideline on improving the accuracy of human epidermal growth factor receptor 2 (HER2) testing for breast cancer patients.

The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) have published a clinical practice guideline on improving the accuracy of human epidermal growth factor receptor 2 (HER2) testing for breast cancer patients. Predictive and prognostic markers are being increasingly used to guide therapy selection, and accurate identification of the HER2 status is key to identifying patients that could benefit from specific treatments, while identifying others that could be spared potentially toxic and costly therapies. This is the first time that these two organizations join forces to address a critical issue that affects all patients with a new diagnosis of invasive breast cancer.

"As molecular testing and pharmagenomics advance, pathologists and clinicians must work together to develop effective practice guidelines for the testing and treatment of patients. Testing for HER2 expression in breast cancer is a perfect example of this," said Elizabeth Hammond, MD, FACAP, co-lead author of the guideline and pathologist at LDS Hospital and Professor of Pathology, University of Utah School of Medicine. "These new HER2 guidelines are a tremendous step forward. They provide practical guidance for the medical laboratory community on how this testing should be conducted and reported. This will help ensure that patients receive the most appropriate, most effective treatment available."

Complementary Tests

The two methods most commonly used to test for HER2 are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). IHC testing can show how much of the HER2 protein is present on the surface of tumor cells, while FISH testing measures the number of HER2 gene copies in the nucleus of each cell. This gene is responsible for high levels of expression of the HER2 protein on the tumor cells.

The guideline recommends a testing algorithm that defines positive, negative, and equivocal values for both the IHC and FISH tests. Equivocal results form a new category and require repeat testing or the use of a different test. The guideline does not recommend initial use of one test over another in general circumstances (special circumstances may lead to the recommendation of one test over another), but recommends strategies to ensure that all tests are correctly performed, validated, and reproducible.

The guideline also recommends that laboratories adhere on stringent quality improvement standards including assessment of HER2 testing concordance of 95% with another validated HER2 test for both positive and negative assay values, participation in ongoing internal testing performance evaluation, and participation in external knowledge testing (proficiency testing). Biannual examination of these activities will occur through laboratory accreditation by a valid accrediting agency like CAP.

"Based on available data, the Panel did not recommend one test over another but focused its efforts on improving the accuracy of HER2 testing, regardless of the test used," said Antonio C. Wolff, MD, FACP, co-lead guideline author and Associate Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. "Because the results of HER2 testing can predict a patient's likely response to different treatments, including chemotherapy, hormone therapy, and trastuzumab [Herceptin], it is crucial that testing with IHC and/or FISH produces accurate results, especially if it is being used as the sole determinant of therapy selection."

HER2 Proficiency Testing

As a result of the panel's recommendations, CAP will require all of the laboratories it accredits to participate in HER2 proficiency testing if they wish to conduct HER2 testing. Proficiency testing deficiencies can result from improper use of a test system, through improper calibration of the test system, or unacceptable precision.

HER2 proficiency testing will include a series of specimen challenges that are sent to laboratories for testing a few times a year. Findings will be reported back and then graded to determine performance. Failure to perform adequately on proficiency testing can result in the laboratory being asked to cease testing until the cause of the failures is identified and corrected. CAP-accredited laboratories also will be required to adhere to the rest of the guidelines when conducting and reporting HER2 testing. These guidelines are intended for use with both types of HER2 testing currently in use. It is hoped that other accrediting agencies will swiftly adopt similar accreditation standards.

"The collaboration between CAP and ASCO has resulted in tangible improvements to the way HER2 testing should and will be conducted, and those improvements will have a direct positive impact on the treatment of patients," said Dr. Hammond. "These new accreditation and proficiency testing requirements for CAP-accredited labs reflect the expanding role laboratories play in not only the diagnosis of disease, but also in the treatments that patients receive. These guidelines are a real victory for patients."

For a copy of the guideline, visit www.jco.org or www.cap.org, call 703-299-1180, or e-mail: guidelines@asco.org.