Abstract 4392: Expression landscape of trophoblast cell surface antigen 2 (Trop-2) in breast cancer
Authors: Song Kai , Yoon Oh Kyu , Zhuo Luting , Elboudwarej Emon , Li Biao , Boice Jillian , Pan Yang , Phan See , Motwani Monica 
Published: April 2023

Background: Antibody-drug conjugates (ADCs) are novel agents linking potent payloads to antibodies targeting antigen-expressing tumors. Sacituzumab govitecan (SG), a Trop-2-directed ADC, is approved for patients with metastatic triple-negative breast cancer (mTNBC) with ≥2 prior therapies (≥1 in metastatic setting). SG is also being investigated in other breast cancer subtypes, including hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and in earlier lines of treatment. To understand the landscape of Trop-2 expression and potential clinical actionability of Trop-2 and other antigens, we evaluated RNA expression data in breast cancer from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC).

Methods: TCGA and METABRIC datasets were assessed for Trop-2, HER2, and programmed death ligand 1 (PD-L1) expression via processed RNA sequencing (RNA-seq) and microarray data of the corresponding genes TACSTD2, ERBB2, and CD274. Gene expression across clinical parameters was assessed via one-way ANOVA, t-test, or Spearman correlation. HER2 status was classified as HER2 immunohistochemistry (IHC) 0 or HER2-low (IHC1+, or IHC2+ and in situ hybridization-negative). Survival was estimated via Kaplan-Meier method. Neoadjuvant therapy datasets were assessed for effects of aromatase inhibitors on Trop-2 expression.

Results: RNA-Seq data was available from 1030 and 2136 breast cancer patients in TCGA and METABRIC datasets, respectively. Most patients (96%) had high TACSTD2 expression (&gt;100 transcripts per million [TPM]). TACSTD2 expression was comparable by breast cancer histology (median log2TPM 6.8-7.5), by disease stages I-IV (median log2TPM 7.0-7.5), or by subtypes (median log2TPM 7.1-7.3). TACSTD2 expression was not correlated with ERBB2 (Spearman rho=0.06) or CD274 (Spearman rho=-0.13) expression. No difference in TACSTD2 expression was noted between HER2 IHC0 or HER2-low subtypes. TACSTD2 expression was not associated with survival, though low tertile TACSTD2 groups had better prognosis in the basal subtype; treatments were heterogeneous. Changes in TACSTD2 gene expression were not observed post-aromatase inhibitors.

Conclusions: While SG is approved for use in mTNBC, TACSTD2 is stably expressed across all breast cancer stages and subtypes, including HER2 IHC0 and HER2-low, and across all ranges of PD-L1 expression, suggesting a broad patient population may benefit from Trop-2-directed ADCs.

Citation Format: Kai Song, Oh Kyu Yoon, Luting Zhuo, Emon Elboudwarej, Biao Li, Jillian Boice, Yang Pan, See Phan, Monica Motwani. Expression landscape of trophoblast cell surface antigen 2 (Trop-2) in breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4392.