The College of American Pathologists ( CAP ) and the American Society of Clinical Oncology ( ASCO ) have issued a joint, updated guideline aimed at improving the accuracy and reporting of human epidermal growth factor receptor 2 ( HER2 ) testing in patients with invasive breast cancer.
The guideline update is based on a systematic review of medical research literature, providing oncologists and pathologists with detailed recommendations for how to test for HER2 overexpression, interpret the results, and recommend HER2-targeted therapies.
Approximately 15% of all newly diagnosed breast cancers are HER2-positive, meaning that the tumors have extra copies of the HER2 gene and/or high levels of the HER2 protein, which controls breast cancer cell growth and spread. HER2-positive tumors usually grow faster compared to HER2-negative tumors.
The purpose of HER2 testing is to identify patients who could benefit from effective HER2-targeted therapies, such as Trastuzumab ( Herceptin ), Lapatinib ( Tykerb ), Pertuzumab ( Perjeta ), and T-DM1 ( Kadcyla ). These treatments can substantially improve survival in patients with HER2-positive invasive breast cancer. It is therefore important to accurately determine the HER2 status to ensure that patients most likely to benefit are offered a HER2-targeted treatment. At the same time, those that are unlikely to benefit can avoid side effects and costs associated with those drugs.
The two FDA-approved methods currently used in the United States to test for HER2 are immunohistochemistry ( IHC ) and in-situ hybridization ( ISH ).
IHC testing assesses how much HER2 protein is present on the surface of tumor cells, whereas ISH testing measures how many copies of the HER2 gene are present inside each cancer cell.
The original guideline focused on IHC and fluorescence in-situ hybridization ( FISH ), whereas the updated guideline adds recommendations for a newer diagnostic technique known as bright-field ISH. This technique also evaluates for amplification of the HER2 gene, and uses a regular light microscope rather than a fluorescent microscope. Some sources of variability may be reduced with this technique as the invasive component can be more easily identified using bright-field microscopy.
The guideline recommends the following:
Always test HER2 status on all newly diagnosed invasive breast cancers ( primary site and/or metastatic site ).
Ensure that at least one tumor sample is tested for either HER2 protein expression ( immunohistochemistry [ IHC ] assay ) or ( in situ hybridization [ 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.
According to M. Elizabeth H. Hammond, co-chair of the ASCO/CAP HER2 Testing in Breast Cancer Panel and at the University of Utah School of Medicine, the number of patients with equivocal HER2 test results used to be rather large. But evidence suggests that the quality of HER2 testing is improving and the frequency of equivocal and inaccurate results is decreasing. ( Xagena )
Source: College of American Pathologists, 2013