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• W4282937269 abstract "Abstract Background: Breast cancer (BC) is one of the three most common cancers worldwide, which is a heterogeneous group of different disease subtypes, each with its own biology and clinical characteristics. Approximately 60% of patients with early-stage BC receive adjuvant treatment, however, only a small number derive a benefit. Recurrence remains a major obstacle. Comprehensive profiling analysis in early-stage (T1-2N0-1M0) BC with different disease subtypes might help understand the tumorigenesis mechanisms and pave the way to evaluate the recurrence risk in early-stage BC. Methods: A total of 418 patients diagnosed with early-stage BC were enrolled, including 82 patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) BC, 49 HR-/HER2+ patients, 239 HR+/HER2- patients, and 48 HR-/HER2- patients. Capture-based targeted sequencing was performed on tumor tissue samples using a panel consisting of 520 cancer-related genes. The genomic profiling among different disease subtypes were investigated and tumor mutational burden (TMB) was calculated. Results: Besides HER2, TP53, CDK12, and PIK3CA were the most frequently mutated genes in both HR2-/HER2+ (75.5%, 65.3%, and 36.7%) and HR2+/HER2+ BC (67.1%, 57.3%, and 36.6%). PIK3CA and TP53 were also the most frequently mutated gene in both HR-/HER2- (22.9% and 81.3%) and HR+/HER2- (54% and 23.4%) BC. Moreover, alterations in KRAS (12.5%) and GATA3 (26.8%) were frequently occurred in HR-/HER2- and HR+/HER2- BC, respectively. Furthermore, a comparable TMB level was observed among four subtypes (median TMB: 3.0 mutations/Mb for HR+/HER2- BC; 3.7 mutations/Mb for other subtypes). Next, the genomic profiling was compared between T1-2N0 and T1-2N1 disease in four subtypes, respectively. No different mutation frequencies in cancer-related genes were observed between T1-2N0 and T1-2N1 disease in both HR+/HER2+ and HR-/HER2- BC. In HR+/HER2- BC, T1-2N1 disease had a higher mutation frequency of TRRAP (4% vs. 0%, p&lt;0.05) and a lower mutation frequency in CHD4 (0% vs. 6%, p&lt;0.01), ERBB3 (0% vs.5%, p&lt;0.05), and CTCF (1% vs.6%, p&lt;0.05) than T1-2N0 disease. In HR-/HER2+ BC, patients with T1-2N1 disease had more alterations occurring in HNF1B (23% vs. 0%, p&lt;0.05) and CDK12 (77% vs.48%, p&lt;0.05), and less alterations occurring in NCOR1 (0% vs. 13%, p=0.096) than those with T1-2N0 disease. Moreover, a higher mutation frequency in homologous recombination signaling pathway was associated with the presence of node metastases in HR-/HER2+ BC (52.2% vs. 76.9%, p=0.082). A comparable TMB level was observed between T1-2N0 and T1-2N1 in four subtypes, respectively. Conclusions: Our work reveals the molecular heterogeneity among four subtypes, and between T1-2N0 and T1-2N1 disease in a certain subtype. These findings suggest that molecular features may also need to be taken into consideration for recurrence risk assessment in early-stage BC. Citation Format: Bo Chen, Yingzi Li, Yuchen Zhang, Guochun Zhang, Haiwei Du, Dailin Sun, Junjun Li, Ning Liao. The comprehensive genomic profiling in early-stage (T1-2N0-1M0) breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5918." @default.
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• W4282937269 date "2022-06-15" @default.
• W4282937269 modified "2023-10-07" @default.
• W4282937269 title "Abstract 5918: The comprehensive genomic profiling in early-stage (T1-2N0-1M0) breast cancer" @default.
• W4282937269 doi "https://doi.org/10.1158/1538-7445.am2022-5918" @default.
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