The Genomic Landscape of Chinese Breast CancerBackground : The comprehensive genomic profiling (CGP) through next-generation sequencing (NGS) brought a new understanding of breast cancer and provided more information about further clinical treatment. However, the genomic features in Chinese breast cancer group are limited to date, which might offer both prognostic and predictive values.

Patients and Methods: Hybrid capture-based CGP was performed on 126 primary and 38 relapsed/metastatic breast cancer patients using a 324-gene panel assay (FoundationOne CDx) to identify all classes of genomic alterations, including base substitutions, insertions and deletions, rearrangement and copy number changes. Tissue samples were obtained by surgery or biopsy.

Results:There was no sample with unstable microsatellite status both in primary and relapsed/metastatic breast cancer patients. The tumor mutational burden was higher in Relapsed/metastatic breast cancer than in primary breast cancer (2.91±0.29 for primary, 5.10±0.50 for relapsed/metastatic breast cancer, respectively, p<0.001). There were 11 genes detected more than 10% incidence across all samples, including TP53(63.69%), PIK3CA(38.85%), ERBB2(22.29%), RAD21(17.20%), CCND1(15.29%), FGF3(14.01%), FGF19(14.01%), MYC(13.38%), NSD3(WHSC1L1)(11.36%), ZNF703(10.83%), among which RAD21, NSD3(WHSC1L1) were novel significantly mutated genes in Chinese breast cancer patients other than the previous genes identified in other ethnic groups and might be related to poor prognosis. The 10 top genes with greater difference mutational incidence between primary and relapsed/metastatic breast cancer were mostly identified in relapsed/metastatic group frequently (TP53, MYC, RAD21, PTEN, MLL2, CCND1, RB1), only 3 gene occurred more often in primary group (PIK3CA, FGFR1, MDM2). Relapsed/metastatic breast cancer patients were probably to get instruction in targeted therapies than primary group from CGP, the proportion of relapsed/metastatic breast cancer patients getting instruction in one or more targeted therapies was 94.74%, whereas the proportion of primary group was 76.98%(p=0.014).

Conclusions:There was significant molecular heterogeneity between primary and relapsed/metastatic breast cancer in Chinese patients and between Chinese and other ethic group.

Fig The mutational landscape of top 21 most frequently mutated genes (mutational incidence >5%) in Chinese breast cancers (n=184). The upper histogram showed the total number of mutations in every patient. The bottom bars indicated the clinical characteristics, samples were grouped by primary breast cancers (n=141) and relapsed/metastatic breast cancers (n=43). Sidebar on the left summarized the mutational incidence of each gene and listed the separate frequencies of primary and R/M patients. Sidebar on the right classified different mutation types.

Citation Format: Qiuting You, Jianli Zhao, Kai Chen, Yi Chen, Minhua Zeng, Biaolin Wen, Linxiaoxiao Ding, Fengxi Su. The genomic landscape of Chinese breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-40.