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.
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.
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.
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.
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.
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.
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.
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.
Authors
Toli Toli, Sarafidis Sarafidis, Filis Filis, Tzoras Tzoras, Tsiknakis Tsiknakis, Sifakis Sifakis, Liatsou Liatsou, Rassidakis Rassidakis, Bergh Bergh, Matikas Matikas, Zerdes Zerdes, Foukakis Foukakis
View on Pubmed