Impact of the Updated Guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) Testing in Breast Cancer

Abstract

Purpose In 2007, the American Society of Clinical Oncology and the College of American Pathologists had established a human epidermal growth factor receptor 2 (HER2) testing guideline, which was updated in 2013 and subsequently in 2018. We assessed the clinical impact of the recent update by comparing the in situ hybridization (ISH) results based on the 2007, 2013, and 2018 guidelines. Methods We assessed 2 cohorts. The first cohort included 1,161 primary invasive breast cancer (IBC) samples including 18 bilateral IBC cases, with both immunohistochemistry (IHC) and silver-enhanced ISH (SISH) results available for the HER2 status. The second cohort included 160 IBC cases with equivocal HER2 IHC, assessed using SISH. We retrospectively evaluated and compared the HER2 SISH results. Results There were 22 (1.9%) and 20 (12.5%) cases with altered SISH results according to the 2013 guidelines in cohorts 1 and 2, respectively. As per the 2018 guidelines, final HER2 statuses of 16 (1.4%) and 14 (8.5%) cases changed in cohorts 1 and 2, respectively. The 2013 guidelines increased the positive rate compared to the 2007 guidelines, in both cohorts (0.6% and 6.2%, respectively). Most equivocal cases in cohorts 1 (92.3%) and 2 (100%) as per the 2013 guidelines were reclassified as HER2-negative according to the 2018 guidelines. The 2018 guidelines increased the negative rates (1.3% in cohort 1 and 8.7% in cohort 2) and slightly decreased the positive rates (−0.2% in cohort 1 and −3.1% in cohort 2), compared to the 2013 guidelines. With each update, minor changes in the positive and negative rates were observed in whole breast cancer samples (cohort 1). However, the 2018 guidelines affected previously defined HER2-positive IBC with equivocal IHC results. Conclusion Under the 2013 guidelines, the positive and equivocal cases increased. However, the 2018 guidelines eliminated ambiguous cases by reclassifying them as HER2-negative.

Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy

“…[18,19] Previous studies indicated that the positive and equivocal cases increased under the 2013 and 2018 guidelines. [20,21] In our study, the proportion of HER2 overexpressing in internal group was lower than external group (28.7% vs. 41.3%). In our study, the proportion of primary tumor response and axillary pCR in external cohort was higher than in retrospective series (34.5% vs. 24.5% and 29.9% vs. 16.1%, respectively).…”

“…We suggested that it might be associated with the changing guideline of HER2 testing recommendation released in 2007, 2013, and 2018 by ASCO/CAP [18,19] . Previous studies indicated that the positive and equivocal cases increased under the 2013 and 2018 guidelines [20,21] . In our study, the proportion of HER2 overexpressing in internal group was lower than external group (28.7% vs .…”