281P - Prevalence of HER2-low breast cancer in the GEICAM/2011-06 trial: Agreement in HER2-low classification between standardized immunohistochemistry assays

Background

Novel anti-HER2 agents in HER2-low breast cancer (BC) may require the re-evaluation of existing assays and a clear characterization of HER2 expression beyond the binary HER2-positive/negative. We aimed to define the frequency of HER2-low in clinical BC by different market standardized HER2 immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) (PathVysion, PharmDx) assays in the GEICAM/2011-06 trial.

Methods

FFPE BC surgical specimens (n=223), enriched in HER2 low expression cases following American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) guidelines for HER2 interpretation, were enrolled in the GEICAM/2011-06 trial to compare local and central HER2 classification, including standardized PATHWAY/4B5 (790-2991 Roche Diagnostics), polyclonal HercepTest (SK001 Dako) and novel monoclonal HercepTest (GE001 Dako Omnis). HER2, HER2-low and HER2 IHC testing status was compared between local and central, as well as within central assessment by different assays, using Kappa index analysis.

Results

Local ASCO/CAP IHC/FISH assessment showed substantial agreement (k=0.70-0.71) with central ASCO/CAP HER2 positive status, but low consensus (k=0.55-0.58) for HER2-low status. Referred to gold standard PATHWAY/4B5 IHC central 2018 ASCO/CAP testing, the monoclonal HercepTest assay enhanced agreement for HER2 status (k=0.95) and HER2-low identification (k=0.75) compared to polyclonal HercepTest (k=0.89 and 0.69, respectively). According to IHC testing, monoclonal HercepTest enhanced agreement with gold standard compared with polyclonal HercepTest, especially for 2+ IHC cases (k=0.57 vs 0.35), but also for 1+ IHC (k=0.51 vs 0.35) and 3+ IHC (k=0.93 vs 0.83) cases.

Conclusions

Local vs central HER2 agreement by standardized IHC techniques decreased for HER2-low compared to HER2 status. Monoclonal HercepTest proved higher agreement with gold standard than polyclonal HercepTest in terms of HER2 status and HER2-low BC identification, especially for 1+ and 2+ IHC cases. This highlights the need for standardized HER2 testing review, particularly when evaluating potential benefits of novel therapies for HER2-low BC patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

GEICAM Spanish Breast Cancer Group.

Funding

Has not received any funding.

Disclosure

F. Rojo: Financial Interests, Personal, Advisory Role: Roche, BMS, MSD, Abbvie, Merck, Novartis, AstraZeneca, Pierre Fabre, GSK, Agilent, Sysmex, Menarini, Amgen, Lilly, Janssen. B. bermejo: Financial Interests, Personal, Invited Speaker: Novartis, lilly, Daichii sankyo, pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Segaen, ROCHE, GILEAD. S. Lopez-Tarruella Cobo: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Gilead, GSK, Roche, Pierre Fabre, Seagen, Menarini_Stemline, Gebro Pharma, Veracyte, MSD; Financial Interests, Personal, Invited Speaker: Lilly; Non-Financial Interests, Member of Board of Directors: GEICAM, SEOM. J.M. Cejalvo: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Lilly, astrazeneca, Gilead. Y. Jerez Gilarranz: Financial Interests, Personal, Invited Speaker: Daichii, Novartis, roche, pfizer. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: Astrazeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarinio-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, Astrazeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, Puma; Non-Financial Interests, Member of Board of Directors: TRIO; Non-Financial Interests, Leadership Role: GEICAM; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Advisory Board: SEOM. All other authors have declared no conflicts of interest.