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The human trophoblast cell-surface antigen 2 (TROP-2) expression on metastasized breast cancer
M Weich1, L Christl2,3, M Kiesel1
1Department of Gynaecology and Obstetrics, University of Würzburg, Josef-Schneider-Str. 4, 97080, Würzburg, Germany.
Purpose:
The antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and datopotamab deruxtecan target trophoblast cell surface antigen 2 (TROP-2) and have shown significant efficacy in HER2-negative metastatic breast cancer (mBC). As TROP-2 may serve as a target across multiple treatment lines, detailed information on TROP-2 expression over time is of great interest.
Methods:
TROP-2 expression was analyzed in breast cancer (BC) samples from patients treated at the University Hospital Würzburg between 2004 and 2025 at clinically indicated biopsy time points (TP), and, in a subset, before and after SG treatment. Expression was assessed immunohistochemically using the H-score (range 0-300).
Results:
We evaluated 229 samples from 76 patients. Overall, patient-level TROP-2 expression was high (mean H-score 241.3 ± 73.2) and largely stable over time (TP1: 235.7 ± 60.8, n = 76; TP2: 244.6 ± 77.4, n = 72; TP3: 245.3 ± 84.4, n = 39; TP4: 244.9 ± 95.6, n = 8). However, 21 patients exhibited a decline in TROP-2 expression during disease progression, defined as a decrease of ≥ 50 H-score points between two consecutive TPs. Among 13 patients with paired biopsies obtained pre- and post-SG treatment, the mean TROP-2 H-score decreased from 227.0 ± 74.6 before SG to 202.9 ± 99.4 after SG (mean change - 24.1 ± 86.0; median 1.7, range - 170 to 110; Wilcoxon p = 0.542). TROP-2 H-score decreased in 6/13 patients and increased in 7/13 patients. Exploratory PFS analysis showed no statistically significant difference by post-SG TROP-2 change (log-rank p = 0.526).
Conclusion:
TROP-2 expression was generally high and relatively stable; however, some patients showed declining levels over time.
Insights
Trophoblast cell surface antigen 2 (TROP-2) expression in metastatic breast cancer is generally high and stable over time. However, some patients show declining TROP-2 levels during disease progression or after sacituzumab govitecan treatment.
Area of Science:
- Oncology
- Translational Research
- Biomarker Analysis
Background:
- Antibody-drug conjugates (ADCs) targeting Trophoblast cell surface antigen 2 (TROP-2), such as sacituzumab govitecan, show efficacy in HER2-negative metastatic breast cancer (mBC).
- Understanding TROP-2 expression dynamics is crucial as it may serve as a target across various treatment lines.
Purpose of the Study:
- To investigate the longitudinal expression patterns of TROP-2 in breast cancer patients.
- To assess TROP-2 expression stability over time and its changes in response to sacituzumab govitecan (SG) treatment.
Main Methods:
- Analysis of 229 breast cancer samples from 76 patients using immunohistochemistry (H-score) at multiple time points.
- Evaluation of TROP-2 expression before and after SG treatment in a subset of patients.
Main Results:
- TROP-2 expression was generally high (mean H-score 241.3) and largely stable across sequential biopsies.
- A subset of 21 patients showed a decline in TROP-2 expression during disease progression.
- In patients treated with SG, TROP-2 H-score showed variable changes post-treatment, with no statistically significant difference in progression-free survival based on these changes.
Conclusions:
- TROP-2 expression in breast cancer is predominantly high and stable over time.
- Individual patient variability exists, with some experiencing decreased TROP-2 levels during progression or post-treatment.
