Impact of the updated 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) gene testing in invasive breast cancers: A single center study

• Published in: Annals of diagnostic pathology Vol. 58; p. 151935
• Main Authors: Lim, Tse Hui, Lim, Alvin Soon Tiong, Tien, Sim Leng, Tan, Puay Hoon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2022
• Subjects: ASCO/CAP; Breast cancer; FISH; HER2; Immunohistochemistry; Immunohistochemistry; FISH; Breast cancer; ASCO/CAP; HER2
• ISSN: 1092-9134; 1532-8198
• DOI: 10.1016/j.anndiagpath.2022.151935

The study aimed to evaluate the impact of the updated 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) testing in invasive breast cancer compared with previous 2013 guidelines. Between Jan 2014 and May 2020, 3364 consecutive invasive breast carcinomas with concurrent HER2 immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) results were retrospectively reviewed for HER2 status. Both 2013 and 2018 testing criteria were applied to establish the HER2 status. The testing algorithms involved testing of invasive breast carcinomas by IHC, with equivocal results being reflexed to FISH assays. Concordance rate improved from 92.7% to 94.1% in the non-equivocal IHC cases with the 2018 guidelines. Comparing 2013 versus 2018 criteria, HER2 non-amplified cases increased significantly from 73.7% (n = 2478) to 76.8% (n = 2585), HER2 amplified cases remained similar from 23.4% (n = 789) to 23.2% (n = 779) while equivocal cases decreased from 2.9% (n = 97) to 0% with the new guidelines. Thus, 107 cases (3.2%) were reclassified from HER2 equivocal (n = 97) and amplified (n = 10) to non-amplified with the updated 2018 guidelines. Under the 2018 criteria, a total of 259 cases (7.7%) belonged to the uncommon categories (groups 2 to 4), with group 3 being the most frequent (4.6%), followed by group 4 (2.9%) and group 2 (0.2%). Implementation of 2018 guidelines resulted in a significant increase in HER2 non-amplified cases, mainly due to the abolishment of the equivocal FISH group. This has helped resolve the clinical practice dilemma by providing a more definitive HER2 gene status. •Improvement in concordance rate for non-equivocal IHC cases with 2018 guidelines•Conversion from HER2 equivocal and amplified to non-amplified in 3.2% of cases•Absent of HER2 status conversion from HER2 non-amplified to amplified•Significant increase in HER2 non-amplified due to elimination of equivocal group.•Increase in cases ineligible for HER2-targeted therapy with 2018 updates.