Abstract P5-06-06: TROP2 and HER2 expression by liquid biopsy in women with mTNBC
Authors: Bourdon David , Cunsolo Alessandra , Guillory Brandon , Slade Megan M. , Caro Giuseppe Di , Tubbs Alisa , Iwase Toshiaki , Ueno Naoto T. 
Published: March 2023

Introduction A blood-based biopsy can inform the prognosis for MBC patients when conventional tissue biopsies are not feasible within often biologically heterogeneous sites of metastatic disease. Several anti-Trophoblast cell-surface antigen 2 (TROP2) and HER2 targeted therapies are now available, either as approved therapy options or in clinical trials for MBC patients. Tumor expression of TROP2 is prominent in metastatic cancers, such as HER2-negative MBC and TNBC, with limited treatment options. Technical feasibility data of blood-based TROP2 and HER2 immunofluorescence assays demonstrate the utility of the Epic Sciences platform for this cohort of metastatic TNBC (mTNBC) patients. Methods Cultured cancer cells (expressing TROP2, HER2, or neither) were added to Healthy Donor (HD) blood, creating the model system used in assay development studies. Blood from 11 confirmed mTNBC patients was collected to analyze this clinically relevant population. Immunofluorescence staining and image analysis were performed on replicate blood-based biopsy slides to assess expression for TROP2 and HER2. CTCs were identified and characterized using Epic Sciences digital imaging and machine learning algorithms. Results Three cancer cell lines of various TROP2 expression levels (HEK293, low; MDA-MB-231, intermediate; and A431, high) exhibited immunofluorescence signal ranges of 168 MFI, 2147 MFI, and 26982 MFI, respectively. A fluorescence cutoff of 218 MFI was established following assay optimization to distinguish TROP2 positive CTCs based on a 95% confidence level. Within the cohort of 11 mTNBC patients, 100% of patients with mTNBC had detectable CTCs. 64% of mTNBC patients had TROP2 positivity (MFI, mean: 1328, range: 37-38281)). On the other hand, 0% of mTNBC patients had HER2 positivity (MFI, mean: 128, range: 40-361)). To date, studies with biomarker expression for these two drugs have been limited to tissue biopsy, which may not always yield contemporaneous sampling in the metastatic setting. These results offer a potential liquid biopsy test identifying pts more responsive to trop2 and her2 directed therapies. Discussion Here we report on a liquid biopsy profile combining protein expression of TROP2 and HER2. Blood-based assessment of TROP2 and HER2 expression is a potential marker for selecting MBC patients likely to respond to anti-TROP2 targeted therapies such as Sacituzumab, or Trastuzumab Deruxtecan has shown to improve survival in mTNBC in the ASCENT trial and DESTINY-04 studies. Recent data on the Destiny-04 trial, which allocated HER2 expressing MBC patients into T-DXd treatment, transformed the definition of TNBC. The development of quantitative, reproducible, and more sensitive immunofluorescence assays is becoming crucial for assigning patients whose disease continually evolves to targeted therapies by increasing clinical trial options. Analysis of the clinical utility of the blood-based cell analysis in guiding patient selection strategies for novel anti-TROP2, HER2, and other targeted therapies treatment in MBC is ongoing.

Citation Format: David Bourdon, Alessandra Cunsolo, Brandon Guillory, Megan M. Slade, Giuseppe Di Caro, Alisa Tubbs, Toshiaki Iwase, Naoto T. Ueno. TROP2 and HER2 expression by liquid biopsy in women with mTNBC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-06-06.