489P - Liquid biopsy with combination of cell & cell-free analysis identifies HER2-expression in patients with metastatic breast cancer

Background

Circulating Tumor Cells (CTCs) are non-invasive diagnostic approaches that can inform treatment decisions for patients with metastatic breast cancer (MBC) when a conventional tissue biopsy is not feasible. Recently, the novel anti-HER2 antibody-drug conjugate, T-DXd, has shown effectiveness against MBCs with low HER2 expression detected by tissue biopsy. In this report, we present data from a comprehensive liquid biopsy platform that includes immunofluorescent HER2 protein expression in CTCs (ctcIF), determination of ERBB2 amplification by single-cell CTC genomics (ctcDNA), and ctDNA alterations in plasma.

Methods

Blood samples were collected from 531 patients with MBC and patient’s HER2 status was determined by the ordering healthcare provider based on previous tissue biopsy results, which were documented on the DefineMBC test requisition form. After isolation, nucleated cells were plated, and slides and plasma were stored in a biobank. CTCs were identified using Epic Sciences digital imaging and machine learning algorithms, and ctcIF allowed for HER2 low determination. ctcDNA was analyzed by low-pass whole-genome sequencing in individual CTCs, and ctDNA alterations were analyzed using a validated NGS panel.

Results

Among the 531 patients, 51% (n=276) were reported HER2 negative but did not have documented HER2 IHC expression, and 15% (n=80) were reported as 0 by IHC from the most recent tissue biopsy. Therefore, 67% (n=356) may not be eligible for T-DXd treatment. Among the 356 patients with unknown IHC status or IHC 0, 93% (331/356) had DefineMBC test results reported to clinicians. DefineMBC identified HER2 expression by ctcIF with no ERBB2 amplification by ctcDNA or ctDNA, which is consistent with HER2-low in 29% (74/258) of patients with unknown IHC status, and 27% (20/73) in patients with HER2 0 by IHC and may indicate for T-DXd treatment.

Conclusions

A liquid biopsy platform combining ctcIF, ctcDNA, and ctDNA with high sensitivity and specificity can determine clinically actionable HER2 expression in MBC that can impact therapeutic decision-making for patients with MBC who do not have documented HER2 IHC expression or HER2 0 by IHC from a previous tissue biopsy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Epic Sciences.

Funding

Epic Sciences.

Disclosure

F. Yan: Financial Interests, Personal, Invited Speaker: Eli Lilly, Grail, AstraZeneca, Gilead. G. Di Caro, E. Lam, K. Horne, R.J. Wenstrup: Financial Interests, Personal, Stocks/Shares: Epic Sciences. All other authors have declared no conflicts of interest.