Assessment of Trophoblast cell surface antigen 2 (Trop-2) expression and its clinical significance in breast cancer: a multi-level analysis of protein and gene expression
In brief
Trop-2 antibody-drug conjugates cut progression risk by two thirds in high-expressing breast cancers
A meta-analysis of three trials found that patients whose tumors had high Trop-2 protein levels experienced about a 67% lower risk of disease progression when treated with Trop-2-directed antibody-drug conjugates versus standard chemotherapy. High Trop-2 expression also correlated with a modestly worse distant recurrence-free interval in early-stage disease, suggesting a prognostic role, but benefits on overall survival were only seen in low-expressing tumors and require further validation.
- Journal
- BMC medicine (Q1)
- Published
- 31 July 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Maria Angeliki Toli, Michail Sarafidis, Panagiotis Filis, Evangelos Tzoras, Nikolaos Tsiknakis, Emmanouil Sifakis, et al.
- PMID
- 42557566
- DOI
- 10.1186/s12916-026-05093-3
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (top studies of the week, 9 August 2026).
Abstract
BACKGROUND: Trophoblast cell surface antigen 2 (Trop-2) is a targetable transmembrane glycoprotein commonly overexpressed in breast cancer (BC). This study combines a systematic review and meta-analysis with a retrospective analysis of an independent early BC patient cohort, aiming to investigate the expression patterns of Trop-2 and their clinical significance in BC. METHODS: A systematic literature search was conducted up to October 2025 to identify studies evaluating Trop-2 protein expression levels and clinical outcomes in patients with BC receiving Trop-2-directed antibody-drug conjugates (ADCs) or chemotherapy. Random-effects meta-analyses were performed to estimate pooled Trop-2 positivity rates and to assess progression-free (PFS) and overall survival (OS) across Trop-2 expression levels. Additionally, an association analysis between Trop-2 protein and gene expression was performed in an early BC patient cohort (n = 564) using immunohistochemistry and gene expression data. Trop-2 protein expression was assessed using both conventional observer-based methods and digital quantitative image analysis. RESULTS: A total of 41 studies fulfilled the inclusion criteria. The overall pooled Trop-2 protein positivity rate was 72% [95% Confidence Interval (CI), 67-77%; 41 studies, n = 9170]. Trop-2-directed ADCs improved PFS versus chemotherapy across different H-score groups, with the greatest benefit in tumours with high H-score [3 studies; n = 575; Hazard Ratio (HR) = 0.33, 95% CI 0.20-0.56, p < 0.0001]. For OS, the benefit was observed in the low H-score group (2 studies; n = 272; HR = 0.75, 95% CI 0.57-0.98, p = 0.034). In the study cohort, Trop-2 protein by observer-read assessment was detected in 396/454 patients (87.22%). Digital pathology identified 54 (11.90%) tumours with low, 326 (71.80%) with medium, and 74 (16.30%) with high H-scores. Observer-read and digital assessments were significantly associated (Pearson's chi-square test, p < 0.001). Higher Trop-2 protein and gene expression were associated with worse distant recurrence-free interval (HRadj = 1.45, 95% CI 1.01-2.08, p = 0.04 and HRadj = 1.33, 95% CI 1.05-1.68, p = 0.02, respectively), particularly in Luminal B subtype. CONCLUSIONS: Trop-2 was detectable across all BC subtypes, exhibiting a wide range of expression levels. Our study suggests that Trop-2 may have a potential prognostic significance in early BC.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.