Genomic alteration profile and PD‐L1 expression among different breast cancer subtypes in Chinese population and their correlations. (20th November 2022)

• Record Type: Journal Article
• Authors: Li, Kai; Cao, Li; Li, Cheukfai; Wu, Jundong; Chen, Bo; Zhang, Guochun; Li, Xueri; Wen, Lingzhu; Jia, Minghan; Wei, Guangnan; Lin, Jiali; Li, Yingzi; Zhang, Yuchen; Mok, Hsiaopei; Ren, Chongyang; Wang, Yulei; Qi, Xiaofang; Guo, Lijie; Che, Yue; Liao, Ning
• Is Part Of: Cancer medicine. Volume 12:Number 5(2023)
• Page Start: 5195
• Page End: 5208
• Publication Date: 2022-11-20
• Subjects: breast cancer -- Ki67 -- next‐generation sequencing -- PD‐L1 -- TMB; 616.994005
• DOI: 10.1002/cam4.5314
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Backgroud: There were limitations existing in programmed cell‐death ligand 1 (PD‐L1) as predictive biomarkers for breast cancer (BC), hence exploring the correlation between PD‐L1 levels and other biomarkers in BC may become a very useful therapeutic clinical tool. Methods: A total of 301 Chinese patients with different BC subtypes including 47 HR+/HER2+, 185 HR+/HER2−, 38 HR−/HER2+, and 31 triple‐negative breast cancer (TNBC) were enrolled in our study. Next‐generation sequencing based Yuansu450 gene panel was used for genomic alteration identification and PD‐L1 expression was tested using immunohistochemistry. Results: The most prevalent BC‐related mutations were TP53 mutations, followed by mutations in PIK3CA, ERBB2, CDK12, and GATA3 in our Chinese cohort. We found that mutations DDR2 and MYCL were only mutated in HR−/HER2+ subtype, whereas H3‐3A and NRAS mutations were only occurred in HR−/HER2− subtype. The percentage of patients with PD‐L1‐positive expression was higher in patients with HR‐/HER2− mainly due to the percentage of PD‐L1‐high level. Mutational frequencies of TP53, MYC, FAT4, PBRM1, PREX2 were observed to have significant differences among patients with different BC subtypes based on PD‐L1 levels. Moreover, a positive correlation was observed between TMB and PD‐L1 level in HR+/HER2− subtype, and showed that the proportion of patients with high PD‐L1 expression was higher than that of patients with low PD‐L1 expression in the HR+/HER2− and HR+/HER2+ cohorts with high Ki67 expression. Conclusions: The genomic alterations based on PD‐L1 and other biomarkers of different cohorts may provide more possibilities for the treatment of BC with different subtypes. Abstract : The mutational alterations based on PD‐L1 levels and the specific mutated genes in the different BC subtype were analyzed. Molecular testing will allow better understanding of disease biology and tailor therapy for specific individual. Verification of using integrated predictive biomarkers for selecting checkpoint inhibitors as a component of combination systemic therapy in BC is ongoing.