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ASCO and College of American Pathologists Issue Guideline for HER2 Testing

doi: 10.1097/01.COT.0000437972.11009.e4


The American Society of Clinical Oncology and the College of American Pathologists have issued a joint, updated guideline for human epidermal growth factor receptor 2 (HER2) testing in patients with breast cancer, designed to improve the accuracy of such testing and its utility as a predictive marker in invasive breast cancer.

The guideline, published online ahead of print in the Journal of Clinical Oncology (doi: 10.1200/JCO.2013.50.9984 ), updates the original 2007 ASCO/CAP guideline recommendation for HER2 testing and is based on a systematic review of the literature and provides detailed recommendations for how to test for HER2 overexpression, interpret the results, and recommend HER2-targeted therapies. The joint guideline was prepared by an ASCO/CAP Update Committee of experts in breast cancer and cancer biomarkers.

“Improvements in testing performance and a better understanding of HER2 biology allowed the panel to tackle less common clinical scenarios, and give clinicians and patients the best possible information to individualize clinical decision-making, and ensure the right treatment is offered to the right patient,” said Antonio C. Wolff, MD, FACP, Co-chair of the ASCO/CAP HER2 Testing in Breast Cancer Panel and Professor of Oncology at Johns Hopkins Kimmel Comprehensive Cancer Center.

HER2-targeted therapies, such as trastuzumab, lapatinib, pertuzumab, and T-DM1, are known to substantially increase survival in patients with HER2-positive invasive breast cancer. Accurate identification of HER2 status ensures that patients most likely to benefit are offered HER2-targeted treatments, and also that those unlikely to benefit can avoid the side effects and costs associated with those drugs.

“Six years ago, our main concern was the unacceptably high number of false-positive test results observed in the first generation of adjuvant trastuzumab trials,” explained M. Elizabeth Hammond, MD, the other Co-chair of the Panel and Professor of Pathology at the University of Utah School of Medicine.

“As a direct result of the 2007 guideline, there has been greater standardization of tissue handling procedures, improvements in laboratory performance of HER2 testing, and the development of more clear reporting criteria for test results. These improvements allowed the panel to update international standards to further improve the accuracy of HER2 testing, and allow all appropriate patients to be considered for HER2-targeted therapies.”

The updated guideline also adds recommendations for the newer diagnostic technique of bright-field in-situ hybridization (ISH), in addition to immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH), both of which were included in the original guideline.

The key recommendations from the guideline are:

  • Always test HER2 status on all newly diagnosed invasive breast cancers (primary site and/or metastatic site)—and ensure that at least one tumor sample is tested for either HER2 protein expression (IHC or ISH assay) for HER2 gene amplification.
  • Discuss the role of HER2-targeted therapy if the HER2 test result is positive and if there is no apparent histopathologic discordance with HER2 testing.
  • Delay the decision to recommend HER2-targeted therapy if the HER2 test result is equivocal. Mandatory retesting should be done on the same specimen using the alternative test if the initial HER2 test result is equivocal or on an alternative specimen.
  • Do not administer HER2-targeted therapy if the HER2 test result is negative. If there is apparent histopathologic discordance with the HER2 test result, additional HER2 testing should be considered.
  • Report a HER2 test result as indeterminate if technical issues prevent one or both tests (IHC and ISH) from being done in a tumor specimen, or prevent the test (or tests) from being reported as positive, negative, or equivocal.
  • Confirm that the testing laboratory conforms to standards set for accreditation by CAP or an equivalent accreditation authority.
  • In rare cases, it may be difficult to know for sure if the result is positive or negative. If additional testing on other tissue specimens is not possible, pathologists and oncologists should consider all available clinical data on the patient prior to recommending HER2-targeted therapy.

More detailed recommendations specifically for oncologists and for pathologists are listed in the guideline.

The updated guideline also emphasizes the critical need for collaboration by all health care providers and organizations involved in the diagnosis and treatment of breast cancer patients, Wolff said via email. “This may turn out to be as simple as picking up the phone, or sending a quick email to discuss a case where a test result may appear to be discordant with clinical scenarios or other standard pathology measures.”

And, the guideline indicates key points for clinicians to discuss with patients regarding HER2 status and includes these recommendations for patient and clinician communication on the topic:

  • Explain the importance of determining the biologic characteristics of breast cancer;
  • Explain the type of tissue used for HER2 testing;
  • Explain the types of test used to determine HER2 status;
  • Explain the interpretation of the HER2 test results;
  • Explain the importance of—when appropriate—retesting HER2 status in new, metastatic tumors; and
  • Explain that HER2 testing guidelines exist.

The guideline, as well as a companion guide, additional clinical tools, and an infographic for patients are available at

© 2013 by Lippincott Williams & Wilkins, Inc.
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