Abstract P2-03-03: The comparison of genomic alteration characteristics of young women with breast cancer between Chinese and Western population
Authors: Liu Hong , Yu Jinpu , Xu Zanmei , Wang Fei , Li Yang , Zhang Siyue , Wang Bin , Yang Beibei , Li Xuesong 
Published: March 2022

Abstract
Background: With the increase in incidence rate of breast cancer, the number of young women with breast cancer (YWBC) is rapidly augmented. As YWBC have practical needs for breast conservation and fertility, they are deserved special attention. Previous study indicated that the proportion of YWBC in China patients with breast cancer was higher than that in Western patients with breast cancer. Objective: The purpose of this study was to evaluate the genomic alteration characteristics in Chinese YWBC when compared to Western YWBC. Methods: Genomic alternations were assessed by targeted next-generation sequencing (tNGS, a 450-gene panel) using breast cancer samples collected from 71 Chinese YWBC (≤35 years old). The data of genomic alternations in Chinese YWBC was compared with that in 200 Western YWBC (≤35 years old) from Memorial Sloan-Kettering Cancer Center (MSKCC) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Results: The median age of the enrolled Chinese YWBC was 31 (20-35) years old. Among them, 42.2% (30/71) were at I-II stages, 46.5% (33/71) were at III-IV stage, and the stage of 11.3% (8/71) patients was unknown. Thirty-one cases were HR+/HER2-, 14 cases were HER2+, 13 cases were triple-negative (TNBC), and the remaining 13 cases were unknown. As for the Western cohort, the median age was 32 (21- 35) years old. Half of the patients (53.0%, 106/200) were I-II stage and 35.5% (71/200) were III-IV stage. Ninety-nine cases were HR+/HER2-, 27 cases were HER2+, 46 cases were TNBC. Top 8 genes with high mutation frequencies in Chinese YWBC were TP53 (60.6%), PIK3CA (39.4%), GATA3 (22.5%), ERBB2 (21.1%), CDK12 (18.3%), MYC (16.9%), FGF19 (15.5%) and FGFR1 (15.5%). Substitution/indel and gene amplification were the common alternation types. In the Western YWBC, TP53 (53.5%), PIK3CA (23.5%), and GATA3 (18.5%) were equally the top 3 mutated genes, whereas ARID1A (7.5%), ESR1 (7.5%), MUC16 (7.0%), PTEN (6.0%), ERBB2 (5.5%) were top 4th to 8th mutated genes, which were different to that in Chinese YWBC. Moreover, 20 mutated genes with significantly different mutation frequencies were screened out in Chinese YWBC when compared to Western patients (P&lt;0.05), including CDK12 (16.9% vs 1.0%, P&lt;0.0001, respectively), MYC (16.9% vs 1.1%, P&lt;0.0001, respectively), FGFR1 (15.5% vs 1.5%, P&lt;0.0001, respectively), FGF4 (11.3% vs 0.50%, P=0.0001, respectively), KMT2C (15.5% vs 2.0%, P=0.0001, respectively). These differentially mutated genes were mainly enriched in longevity pathway, drug resistance pathway and cell cycle related pathway. With further combining with molecular typing analysis, 13 (65.0%) different mutation genes were found to be significantly different in Chinese and Western populations, namely, FGF4, FGFR1, KMT2C, SPEN, CDKN2A, GNAS, NCOR1, NF1, BAP1, NBN, PIK3CA and EGFR. In addition, 13 (18.3%) of Chinese YWBC possessed germline mutations, and 1 of them was present in each patient. Among the 13 germline mutations, 5 were pathogenic and 8 were pathogenic-like. Germline mutations mainly occurred in homologous recombination pathway, including four mutations in BRCA1, two in RAD51D; BRCA2, PALB2, FANCA, FANCC and NBN harboring one mutation each. Germline mutations were unavailable in Western populations. Conclusion: The present study demonstrated that the gene mutation profile was significantly different between Chinese YWBC and Western YWBC, suggesting that different diagnostic and/or therapeutic strategy should be considered in Chinese YWBC when compared to Western YWBC.
Citation Format: Hong Liu, Jinpu Yu, Zanmei Xu, Fei Wang, Yang Li, Siyue Zhang, Bin Wang, Beibei Yang, Xuesong Li. The comparison of genomic alteration characteristics of young women with breast cancer between Chinese and Western population [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-03-03.