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Trop-2 expression as a biomarker of response to sacituzumab govitecan in patients with HER2-negative metastatic breast cancer: A pilot study

Year: 2025

Type: article

Abstract: BACKGROUND: Sacituzumab govitecan (SG) is an anti-Trop-2 antibody-drug conjugate (ADC) approved for use in HER2-negative metastatic breast cancer (MBC). This study explores whether Trop-2 expression serves as a biomarker of excellent response versus non-response to sacituzumab govitecan (SG) in HER2-negative MBC. METHODS: Trop-2 expression was determined from patients with HER2-negative MBC categorized as non-responders and excellent responders to SG. Excellent response was defined by a complete or partial response and a progression-free survival (PFS) greater than the median of the cohort. Non-response was defined by progressive disease within 3 months. Trop-2 expression was determined based on percentage of cells staining and a histochemical score (H-score). RESULTS: Of the 15 patients with HER2-negative MBC (8 non-responders/7 excellent responders), the median Trop-2 expression rate was 100 % in both groups (p=0.3). H-score was also similar between the groups, with a median H-score of 270 (range 25-300) in non-responders and 280 (range 120-290) in responders (p=1.0). Lower Trop-2 percent expression was associated with shorter PFS (hazard ratio [HR]: 0.014; 95 % CI, 0-0.52; p=0.018), although Trop-2 expression by H-score was not predictive of PFS (HR: 0.994; 95 % CI, 0.987-1.002; p=0.12). One non-responder had an H-score of 25, which may represent a complete lack of Trop-2 expression. DISCUSSION: In this study, Trop-2 expression did not predict excellent response versus non-response to SG in patients with HER2-negative MBC. Low Trop-2 expression, as determined by percentage staining, was predictive of shorter PFS, although the same association was not observed using the H-score. A complete lack of Trop-2 expression may predict SG ineffective, which requires further investigation.

Source: Cancer Treatment and Research Communications

DOI: 10.1016/j.ctarc.2025.100954