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.

Authors

Roberto Buonaiuto, Martina Pagliuca, Alessandra Longobardi, Maria Letizia Cataldo, Luca Arecco, Riccardo Gerosa, Gabriella Gentile, Aldo Caltavituro, Ines Barone, Bengisu Karakose, Elisa Agostinetto, Christos Sotiriou, Michelino De Laurentiis, Evandro De Azambuja, Carmine De Angelis

Published in

Journal of the National Cancer Institute. Jul 10, 2026. Epub Jul 10, 2026.

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.

PMID:
42429566
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

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