Impact of trop-2 expression on the efficacy of trop-2-targeted antibody-drug conjugates in metastatic breast cancer: a systematic review and meta-analysis.

Abstract

Trophoblast cell surface antigen 2 (Trop-2) is expressed across multiple tumors, including breast cancer (bc). Antibody-drug conjugates targeting Trop-2 (ADC-T2) have demonstrated efficacy in metastatic bc (mBC). However, the extent to which clinical benefit varies according to Trop-2 expression remains unclear. We conducted a systematic review and meta-analysis (PROSPERO: CRD420251074955) of phase II-III trials (conducted from January 2015 to September 2025), enrolling patients with mBC treated with ADC-T2, to assess the relationship between Trop-2 expression and ADC-T2 efficacy. Hazard ratios (HRs) and 95% confidence intervals (CI) for progression-free survival (PFS) were extracted according to study-defined Trop-2 levels. Pooled HRs were estimated using fixed- or random-effects models based on heterogeneity. Five randomized trials (ASCENT, TROPiCS-02, EVER-132-002, OptiTROP-Breast01 and TROPION-Breast01), including 1,879 patients treated with ADC-T2 or chemotherapy were included. ADC-T2 significantly improved PFS compared to chemotherapy in both Trop-2-high (HR 0.34, 95% CI 0.20-0.57) and Trop-2-low (HR 0.63, 0.50-0.79) subgroups in the overall mBC population and in TNBC (Trop-2-hig: HR 0.27, 0.20-0.37, p < 0.001; Trop-2-low: HR 0.46, 0.33-0.64, p < 0.001). However, in HR+/HER2- mBC, a significant PFS benefit was observed only in the Trop-2-high subgroup (HR 0.56, 0.47 to 0.68, p < 0.001). Across all disease subtypes, the magnitude of PFS benefit was greater in Trop-2-high tumors. ADC-T2 significantly improved PFS mBC but the therapeutic benefit was greater in those with high Trop-2 expression. These findings underscore the importance of standardized, clinically meaningful Trop-2 testing to optimize patient selection and treatment decision-making.