Abstract P5-07-08: The clinical utility of alternative chromosome 17 probes in equivocal HER2 results

Abstract

Abstract Background Acurrate assessment of HER2 status in patients with breast cancer is critical in selecting patients for targeted therapy. In 2013, the American Society of Clinical Oncology-/College of American Pathologists (ASCO/CAP) released new guidelines for HER2 testing in an attempt to more acurately identify all breast cancer patients who are eligible for HER2 targeted therapy; these guidelines included new cutoff points for HER2/CEP17 ratio by in situ hybridization (ISH) or average HER2 copy number/cell and recommended the use of a reflex test with alternative ISH chromosome 17 probe for resolving cases with equivocal HER2 ISH results. We sought to determine the clinical utility of alternative chromosome 17 probes in such equivocal cases. Patients and Methods Our institution's database of HER2 dual- probe ISH results was searched for cases of invasive breast cancer with a HER2/CEP17 ratio of <2 and an average HER2 copy number of >4 and <6 signals/cell (i.e., cases meeting the new ASCO/CAP definition of equivocal). Of these, 30 consecutive cases with available corresponding sections were selected for additional chromosome 17 studies using probes for Smith-Magenis syndrome (SMS) and retinoic acid receptor alpha (RARA) genes. A eusomic copy number exhibited in one or both of these loci was used to calculate a revised HER2/chromosome-17 ratio by using the eusomic gene locus as the reference. Results Of 5489 cases of invasive breast cancer tested by dual-probe ISH for HER2 gene status, 316 (5.7%) cases were found to have equivocal results according to the 2013 ASCO/CAP guidelines. Further analysis of the 30 equivocal consecutive cases using the alternative chromosome 17 probes (SMS/RARA), 17 cases were upgraded from equivocal to positive HER2 status, and 13 cases remained unchanged. Conclusion The use of alternative chromosome 17 probes effectively determines true HER2 status in most equivocal HER2 ISH cases. Equivocal results are common; therefore, we advocate testing for alternative chromosome 17 genes to better categorize equivocal cases under the new ASCO/CAP guidelines. Additional analysis of the remaining equivocal cases and their relation to disease progression is underway and will be presented at the meeting. Citation Format: Sneige N, Gong Y, Multani AS, Ibrahim NK. The clinical utility of alternative chromosome 17 probes in equivocal HER2 results. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-07-08.