Abstract 960: Overlapping expression landscape of antibody drug conjugate targets, trophoblast cell surface antigen 2 (Trop-2) & human epidermal growth factor receptor 2 (HER2), in breast cancer
Authors: Medford Arielle J. , Haradhvala Nicholas J. , Vidula Neelima , Abelman Rachel , Spring Laura M. , Ellisen Leif W. , Getz Gad , Bardia Aditya 
Published: April 2023

Background Antibody drug conjugates (ADC) are novel drugs linking potent payloads to antibodies targeting antigen-expressing tumors. Sacituzumab govitecan (SG), targeting Trop-2, is approved for metastatic triple negative breast cancer (TNBC); and trastuzumab deruxtecan, targeting HER2, is approved for HER2-positive and HER2-low metastatic breast cancer. To understand the potentially overlapping clinical landscape of Trop-2 and HER2 antigens, we evaluated RNA expression data in breast cancer from The Cancer Genome Atlas (TCGA) project.

Methods TCGA dataset was assessed for Trop-2 and HER2 expression via processed RNA sequencing (RNA-seq) data of the corresponding genes TACSTD2 and ERBB2. Medium/high gene expression was assessed as &gt;100 transcripts per million (TPM). Samples were classified HER2-low per ASCO/CAP guidelines. Gene expression across clinical parameters was assessed via one-way ANOVA.

Results 1076 patients with primary breast cancer were included. The majority (59%) had both high TACSTD2 expression (TACSTD2hi) and high ERBB2 expression (ERBB2hi) (see Table). Median TACSTD2 expression was 572 TPM (IQR 349-666 TPM); median ERBB2 expression was 122 TPM (IQR 73-192 TPM). No significant difference was observed in TACSTD2 or ERBB2 expression among invasive ductal carcinoma, invasive lobular carcinoma, mixed histology, or other (p = 0.07, 0.23). No significant difference in TACSTD2 expression was noted between HER2-low and HER2-negative subtypes (p=0.34).

Conclusions While SG is approved in TNBC, TACSTD2 is expressed across all breast cancer subtypes, including HER2-low, suggesting a broader population may benefit from Trop-2-targeted ADCs. Furthermore, given that over half of breast cancers have high expression of both TACSTD2 and ERBB2, additional studies are needed to understand the optimal sequencing of ADC-based therapies for patients with breast cancer.

Table Patient subsets(HR = hormone receptor) n TACSTD2hi & ERBB2hi TACSTD2hi & ERBB2low TACSTD2low & ERBB2hi TACSTD2low & ERBB2low All 1,076 632 (59%) 394 (36%) 19 (2%) 31 (3%) Histology 843 Invasive ductal carcinoma 507 267 (32%) 215 (25%) 10 (1%) 15 (2%) Invasive lobular carcinoma 130 103 (12%) 24 (3%) 1 (&lt;1%) 2 (&lt;1%) Mixed 91 63 (7%) 24 (3%) 2 (&lt;1%) 2 (&lt;1%) Other 115 65 (8%) 43 (5%) 2 (&lt;1%) 5 (&lt;1%) HER2 Status 345 HR+/HER2-low 254 170 (49%) 77 (22%) 6 (1%) 1 (&lt;1%) TNBC/HER2-low 55 12 (3%) 39 (11%) 1 (&lt;1%) 3 (&lt;1%) HR+/HER2-negative 24 13 (4%) 11 (3%) 0 0 TNBC/HER2-negative 12 1 (&lt;1%) 10 0 1 (&lt;1%)

Citation Format: Arielle J. Medford, Nicholas J. Haradhvala, Neelima Vidula, Rachel Abelman, Laura M. Spring, Leif W. Ellisen, Gad Getz, Aditya Bardia. Overlapping expression landscape of antibody drug conjugate targets, trophoblast cell surface antigen 2 (Trop-2) & human epidermal growth factor receptor 2 (HER2), 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 960.