HER2 Testing Guideline Update in Breast Cancer Yields Similar Positivity Rate

The 2013 updates to human epidermal growth factor receptor 2 (HER2) testing guidelines, published by the American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP), did not result in changes to the rate of HER2 positivity among breast cancer patients, according to a new analysis. More repeat tests are now being performed, and more patients have “equivocal” HER2 status, meaning they would not be candidates for HER2-targeted therapy.

The first ASCO/CAP guideline on HER2 testing was released in 2007, and it was updated in 2013. “These latest recommendations focus on maximized identification of patients who may benefit from HER2-targeted therapy and limitation of false-negative results, which may deny patients the best possible treatments,” wrote study authors led by Wedad M. Hanna, MBBCh, of Sunnybrook Health Sciences Centre in Toronto. The update included new definitions of immunohistochemistry (IHC) 3+ score, cutoffs of in situ hybridization (ISH)-positive and –equivocal results, and other changes.

To evaluate how those updates affected HER2 testing and positivity, the researchers compared two groups of patients tested during 2012 and 2014, before and after the update. In total, there were 2,201 patients (2,278 tumors) in the 2012 group, and 2,558 patients (2,659 tumors) in the 2014 cohort. The results of the analysis were published online ahead of print in the Journal of Clinical Oncology.

The rate of HER2 positive remained similar from before and after the update, at 15.7% vs 15.5%, respectively. There were more repeat tests performed within 6 months of the initial test after the update, with 122 performed in the 2012 cohort (5.5%) and 302 in the 2014 cohort (11.8%; P < .001).

There were fewer IHC 2+ tumors found after the update, at 25.3% in 2012 compared with 20.3% in 2014 (P < .001). IHC 3+ was similar between the 2012 (11.8%) and 2014 groups (11.5%).

There were more patients with unresolved HER2 status, meaning equivocal by both IHC and ISH, after the update. The earlier cohort had only four such cases, compared with 90 after the guidelines were updated (P < .001). “The benefit of targeted therapy in this group is not proven,” the authors wrote. “Limitation of the number of patient cases in this category should be addressed in the next iteration of the guidelines by exploration of the available data about various methodologies or techniques to classify them.”