Abstract PS1-09-12: Trop2 expression and therapeutic opportunities in inflammatory breast cancer

Abstract Background: Inflammatory breast cancer (IBC) is a rare and aggressive subtype with poor outcomes, particularly in patients with residual disease post-neoadjuvant therapy. Antibody-drug conjugates (ADCs), such as sacituzumab govitecan (SG), have shown efficacy in hard-to-treat subtypes like TNBC and HR+/HER2- disease. This study aims to establish the consistent expression of TACSTD2 (TROP2) in IBC and evaluate its potential as a therapeutic target and biomarker to improve outcomes in aggressive IBC subtypes. Methods: Both IBC and non-IBC samples were evaluated using BostonGene’s comprehensive transcriptomic analysis platform, which includes RNA-seq data processed through an internally validated pipeline. Morgan Welch IBC Program at MD Anderson Cancer Center Registry and other related protocols were utilized to recruit patients. TROP2 expression levels were quantified and categorized as high, medium, or low. A total of 71 IBC samples from this cohort then were compared with 631 non-IBC samples, including non-IBC of no special type (NST), non-IBC TNBC, and PAM50 subtype-matched non-IBC (basal-like, luminal, and HER2-enriched). Univariate analyses were conducted to assess differences in TROP2 expression across these groups. To evaluate clinical relevance, progression-free survival (PFS) was analyzed in a subset of patients (n=11) treated with SG. Results: There was no statistically significant difference in TROP2 expression between IBC and non-IBC samples when compared as whole group. In subtype-matched comparisons, no statistically significant differences were observed, although 15 of 22 basal-like IBC samples had TROP2 expression above the median of basal-like non-IBC. TROP2 expression did not differ significantly between HR+ and TNBC subtypes (p = 0.6657), and while TNBC patients had numerically longer PFS (mean: 1048.4 days) compared to HR+ patients (906.8 days), the difference was not statistically significant. PFS while treated with SG was longest in high expressors (mean: 1142.0 days), followed by medium (994.7 days) and low expressors (983.0 days); however, the correlation coefficient between TROP2 expression and PFS was negligible (r = 0.084). Conclusion: Our study supports further investigation of the role of TROP2 in IBC and its potential in therapeutic development for this rare, aggressive subtype of breast cancer. Although no significant correlation was found between TROP2 expression and PFS among SG-treated patients, TROP2 alone may not serve as a reliable predictive biomarker in this population. Notably, this univariate analysis did not account for confounding variables such as age, race, histology, stage, or prior treatments. Future studies using multivariate models could better isolate the impact of transcriptomic TROP2 expression. Given the limited surface targets in TNBC and HR+/HER2− subtypes and the relatively consistent expression of TROP2, incorporating it into a multi-marker predictive model may enhance patient selection for TROP2-targeted therapies like SG. Acknowledgement: The transcriptomic analyses were performed via collaboration with BostonGene and MW IBC program. Morgan Welch IBC Research and Clinic Program is funded by the State of Texas Rare and Aggressive Breast Cancer Grant. Citation Format: S. Murray, A. Nasrazadani, C. Yam, A. Alexander, O. Baranov, D. Goncharova, F. Paradiso, M. Hensley, The MDACC Inflammatory Breast Cancer Team, W. A. Woodward, R. Layman, S. Saleem, V. Valero, M. C. Stauder, A. Lucci, S. X. Sun, G. J. Whitman, M. Patel, H. Le-Petross, Y. Lu, A. Marx, C. Yajima, M. Kai, L. Villarreal, H. Lopez, B. Lim. Trop2 expression and therapeutic opportunities in inflammatory breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-09-12.