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