Abstract 14P
Background
Recently, a HER2-targeting antibody-drug conjugates (HER2-ADC) was approved to treat HER2-low breast cancer (BC), currently defined by the immunohistochemical (IHC) HER2-expression ASCO/CAP scores of 1+ or 2+ without HER2/ERBB2 amplification. While the HER2 IHC assay was optimized to detect protein overexpression, concerns exist regarding the use of this assay to reliably detect HER2-low BC. Here, we aimed at investigating the correlation between the IHC classification and the tumor cell expression levels of ERBB2 mRNA at the single cell level.
Methods
We retrospectively analyzed 22 untreated BC samples with single cell RNA-sequencing and centralized HER2 IHC data. IHC staining for HER2 (Agilent, GA0485, RTU) was performed and scored according to ASCO/CAP 2018 guidelines. Single cell data were retrieved from the original publication (PMID: 33958794) and only the cancer cells (n= 31016) were retained. ERBB2 expression was considered among cells where ERBB2 could be detected (non-zero normalized expression).
Results
We identified 1 HER2-zero (with no staining on tumor cells), 16 HER2-low (4 HER2-1+, 12 HER2-2+ FISH-negative) and 5 HER2-positive samples. The median percentage of cells expressing ERBB2 per patient was 38% (8%, 34%, 46% in HER2-zero, low, and positive respectively). Median ERBB2 expression was 0.94 (range: [0.13-5.27]) overall (0.48, 0.90, 2.8 in HER2-zero, low, and positive, respectively). Intra-patient heterogeneity of ERBB2 expression was observed with a median IQR of 0.63 overall (0.49, 0.63, 0.94 in HER2-zero, low, and positive, respectively). 36% (27/74) of the ERBB2 expressing tumor cells in the HER2-zero tumor had an ERBB2 expression value equal or greater than the 25th percentile of the ERBB2 expression observed in HER2-low cells. When considering the ER IHC status, the percentage of expressing cells was higher in ER-positive samples but the level of ERBB2 expression was similar.
Conclusions
Single cell data might provide more granularity into the tumor-specific expression levels of HER2. Future research is needed to investigate whether single-cell ERBB2 expression could serve as a predictive biomarker for HER2-ADC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Wildiers: Financial Interests, Institutional, Advisory Board: Roche, Lilly, AstraZeneca, Daiichi Sankyo, PSI Cro AG, KCE, MSD, MSD, E Squared Communications LLC; Financial Interests, Institutional, Invited Speaker: Eisai, AstraZeneca; Financial Interests, Institutional, Other, Consultancy fee: AbbVie, Immutep Pty; Financial Interests, Institutional, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Other, Consultancy: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Grant to the Leuven Breast Center to support the research database: Roche; Financial Interests, Institutional, Research Grant, Grant to institute to perform a multicentric national academic trial: Novartis; Other, Travel & accomodations: Pfizer; Other, Travel & accomodation: Roche; Other, Subscription fee: Gilead. K. Punie: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Roche, Vifor Pharma, Eli Lilly, Pierre Fabre, McCann Health, Roularta, Teva, Gilead Sciences, Pfizer, Gilead, MSD; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche, Novartis, Eli Lilly, Mundi Pharma, MSD, Medscape, MSD; Financial Interests, Institutional, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Gilead, Novartis, MSD, Roche; Financial Interests, Personal, Invited Speaker: Sanofi, AstraZeneca; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Institutional, Funding: Sanofi; Non-Financial Interests, Principal Investigator: EORTC 1745-ETF-BCG trial; Non-Financial Interests, Other, Committee member: ESMO Young Oncologists Committee; Non-Financial Interests, Invited Speaker: BSMO; Non-Financial Interests, Other, Committee Member: ESMO Resilience Task Force; Non-Financial Interests, Advisory Role: Commission personalized medecine Federal Government Belgium; Non-Financial Interests, Advisory Role, External Scientific Advisor: European Medicine Agency. G. Floris: Financial Interests, Institutional, Advisory Board, paid to institution: AstraZeneca. All other authors have declared no conflicts of interest.