Abstract 212P
Background
ERBB2 alterations are potential candidates for targeted treatments in metastatic urothelial cancer (UC). Recent data suggest that HER2-targeted antibody-drug conjugate (ADC) treatment is efficacious. Here, we explore the role of ERBB2 in UC by analyzing genomics in a large database of real-world patients.
Methods
Tumor tissues from 1112 Chinese patients with UC were evaluated by comprehensive genomic profiling for alterations in 808 cancer-related genes. Results were analyzed for base substitutions, short indels, copy number changes, and selected rearrangements.
Results
Of 1112 cases, 167 (15.0%) featured ERBB2 genomic alterations (GAs), including 82 (7.4%) ERBB2 mutations (ERBB2mut), 41 (3.7%) ERBB2 amplifications (ERBB2amp) and 44 (4.0%) cases had co-occurring ERBB2 GAs. ERBB2mut was not mutually exclusive of ERBB2amp which occurred in up to 43.2% of co-altered cases. The top mutated ERBB2 SNVs/indels were p.S310F/Y (32, 21.2%) and p.L755S (7, 4.6%). ERBB2mut predominantly affected the kinase (49, 32.5%) or extracellular (69, 45.7%) domains. Genes commonly co-altered with ERBB2 were TERT (68.9%), ARID1A(37.1%), RB1 (28.7%), KMT2C (26.9%) and ATM (24.6%). Other significantly higher mutation frequency for genes were TP53, APC, SMARCA4, NF1, ERBB3, ERCC2, EGFR and MTOR (p＜0.05) in ERBB2 GAs cases. Significantly lower rates of CDKN2B were found in ERBB2 GAs compared with ERBB2 wild type (22.0% vs 12.0%, p＜0.01). CDK12 was the most common co-amplification gene with ERBB2amp (p＜0.01). FGFR3 mutations were significantly enriched in ERBB2mut than ERBB2amp (p=0.04). Patients with ERBB2 GAs were significantly more likely to have high tumor mutational burden (p＜0.01).
Conclusions
The study provided the landscape of ERBB2 alterations in UC that may benefit from anti-HER2 agents. Consideration should be given to developing trials inclusive of patients with UC harboring ERBB2 alterations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5P - Clinicopathologic features and genomic profiling of occult breast cancer
Presenter: Liansha Tang
Session: Poster Display
Resources:
Abstract
6P - Tumor cell-released autophagosomes (TRAPs) promote lung metastasis through inducing PD-L1 high expression of pulmonary vascular endothelial cells (PVECs) in breast cancer
Presenter: Xuru Wang
Session: Poster Display
Resources:
Abstract
7P - Tumor cell-released autophagosomes (TRAPs) promote breast cancer lung metastasis by modulating neutrophil extracellular traps formation
Presenter: Xiaohe Zhou
Session: Poster Display
Resources:
Abstract
9P - Clinicopathological features and prognosis of mucinous breast cancer: A retrospective analysis of 358 patients in Vietnam
Presenter: Hoai Hoang
Session: Poster Display
Resources:
Abstract
10P - Comparison of 28-gene and 70-gene panel in risk-prediction of Chinese women with early-stage HR-positive and HER2-negative breast cancer
Presenter: Lei Lei
Session: Poster Display
Resources:
Abstract
11P - Multimodal analysis of methylation and fragmentomic profiles in plasma cell-free DNA for differentiation of benign and malignant breast tumors
Presenter: Hanh Nguyen
Session: Poster Display
Resources:
Abstract
12P - Plasma cell-free mRNA profiles enable early detection of breast cancer
Presenter: Chi Nguyen
Session: Poster Display
Resources:
Abstract
13P - Relationship of distress and quality of life with gut microbiome composition in newly diagnosed breast cancer patients: A prospective, observational study
Presenter: Chi-Chan Lee
Session: Poster Display
Resources:
Abstract
14P - Classification of molecular subtypes of breast cancer in whole-slide histopathological images using a novel deep learning algorithm
Presenter: Hyung Suk Kim
Session: Poster Display
Resources:
Abstract
15P - The regulation of pregnenolone in breast cancer
Presenter: Hyeon-Gu Kang
Session: Poster Display
Resources:
Abstract