New ASCO/CAP guideline recommendations for HER2 testing increase the proportion of reflex in situ hybridization tests and of HER2 positive breast cancers.

Accurate determination of tumour human epidermal growth factor receptor type 2 (HER2) status is critical for optimal treatment of breast cancer. In October 2013, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) issued joint updated guideline recommendations for HER2 testing in breast cancer, with a revised algorithm for interpretation of immunohistochemistry (IHC) and in situ hybridisation (ISH) results. This study investigates the impact on HER2 IHC categorisation, implication for reflex ISH testing and potential for identification of false negative IHC. HER2 IHC preparations on 251 invasive breast tumours, originally reported according to 2007 guidelines, were re-scored using 2013 guidelines and the diagnostic categories compared. The results of ISH testing on a separate cohort of 32 breast tumours reported as HER2 IHC 2+ following the introduction of the 2013 guidelines, that would have been designated 1+ according to 2007, were reviewed. Application of 2013 guidelines resulted in a decrease in tumours classified as HER2 negative (83/251 vs 144/251) and a comparable increase in those classified as equivocal (2+) (139/251 vs 80/251). Relatively few tumours were re-classified as positive (29/251 vs 27/251). Furthermore, 3/32 breast cancer cases (HER2 IHC 2+ as per 2013 guidelines, 1+ using 2007 guidelines) were HER2 ISH positive. Application of the 2013 guidelines increases the HER2 IHC equivocal (2+) category and requirement for reflex ISH testing. The reduced threshold for ISH testing identifies some patients with HER2 positive breast cancer whose tumours would have been categorised as HER2 negative according to the 2007 guidelines.