The American Society of Clinical Oncology and the College of American Pathologists recently issued new clinical practice guidelines for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. The new recommendations include a number of significant changes from the previous guidelines, which were first published in 2007 and last updated in 2013.
HER2 gene amplification predicts responsiveness to HER2 targeted therapies and is determined by in situ hybridization (ISH) and protein overexpression indicated by immunohistochemistry (IHC). Since the original recommendation were issued, the number of false-positive HER2 test results have dropped substantially.
Guideline recommendations. Source.
The expert panel addressed three questions:
What is the most appropriate definition for immunohistochemistry 2+ (IHC equivocal)? The new definition of IHC equivocal is invasive breast cancer that show weak to moderate complete membrane staining in more than 10% of tumor cells.
Must HER2 testing be repeated on a surgical specimen if initially negative test on core biopsy? “If the initial HER2 test results in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may be ordered on the excision specimen.” Circumstance that might call for retesting include a grade 3 tumor. The previous guidelines mandated retesting.
What is the optimal algorithm for less common patterns observed when performing dual-probe in situ hybridization testing in breast cancer? The guidelines addressed three scenarios (dual-probe ISH group 2, 3 and 4) which together affect less than 5% of cases. Overall, they call for more rigorous interpretation criteria for ISH, including a recount by a blinded observer and adjudication, if necessary. The guidelines also require IHC review of the same tissue sample and concomitant review of the IHC and ISH slides to determine which areas to select for ISH scoring and the most accurate HER2 status designation. The panel also recommended that all laboratories using single-probe ISH assays also include IHC review with their results.