Background: Trophoblast antigen 2 (Trop2) is a glycoprotein expressed by many cancers. A phase I study of the trop2 antibody drug conjugate (ADC) IMMU-132 has shown promising activity in triple negative (TN) BC. We studied associations of primary BC trop2e with clinical characteristics, outcomes, and selected genes in publically available databases.
Methods: Trop2e was evaluated with microarray data from the neoadjuvant I-SPY 1 (n=149), METABRIC (n=1992) & TCGA (n=817) databases. Associations with clinical features were assessed with the Kruskal-Wallis test (all). Correlations with chemotherapy response were evaluated with the Wilcoxon rank sum test (I-SPY 1) & with recurrence free survival (RFS) by the Cox proportional hazard model (I-SPY 1 & METABRIC). Pearson correlations were used to study associations between trop2e & selected genes (all).
Results: In all 3 datasets, trop2 was detectable and had a wide range of expression in all BC subtypes. In I-SPY 1, trop2e did not vary by hormone receptor (HR) & HER2 or intrinsic subtype; in METABRIC & TCGA trop2e was lower in HER2+ than HR+/HER2- & TNBC (METABRIC p=0.03, TCGA p=0.007) & in HER2+ enriched and luminal B BC (p < 0.001, METABRIC & TCGA). Trop2e was higher in grade I vs. II/III BC in METABRIC (p < 0.001). No association with chemotherapy response was seen (I-SPY 1) or with RFS (I-SPY 1 & METABRIC). The table below shows significant (p<0.05) gene correlations with trop2e in ≥2 datasets.
Conclusions: Trop2e is seen in all BC subtypes, particularly luminal A and TNBC. Trop2e correlates with the expression of genes involved in cell epithelial transformation, adhesion, and proliferation and inversely with immune genes, which may contribute to tumor growth. These findings support the use of trop 2 directed ADC in all BC subtypes.