Abstract 5772: Differences in clinical actionability by comparing mutational landscape of young and old breast cancer patients

Abstract

Abstract Background: Early-onset breast cancer (BC) is associated with poor prognosis, which is also characterized by high recurrence risk, distant metastases and advanced stages at the time of diagnosis. While germline mutations in BRCA1/2 are known to underlie a subset of early-onset BC cases, the clinical and genetic characteristics in other young BC patients remain to be explored. Method: We profiled primary lesions from 440 Chinese female BC patients by using a 425-cancer-gene panel. The population was sub-divided into young (≤40 years old) and old (>40 years old) BC patients according to ages at diagnosis. Young and old BC patients were compared for their associations with genomic aberrations, with focus on existing BC targetable alterations, including those in the ERBB2 gene and PI3K and homologous recombination repair (HRR) pathways. Results: 137 (31.1%) patients presented with BC at a young age (median age=35 [18-40]) and 303 (68.9%) with BC diagnosed at an older age (median age=53 [41-82]) in our study cohort. TP53 (young, 61.3%; old, 67%), PIK3CA (33.6% and 41.3%), and GATA3 (9.5% and 8.3%) were among the top frequently altered genes in both subgroups. A total of 70 patients carried pathogenic germline mutations. Of these, 57.3% were alterations in the HRR pathway genes, including BRCA1/2, WRN, BLM, and PALB2, etc, with comparable frequencies in young and old patients. Germline BRCA1/2 mutations were detected in nine (6.6%) and 23 (7.6%) of the young and old patients, respectively. Somatic BRCA1/2 mutational frequencies were also comparable between young (8.8%) and old (9.9%) patients. Overall, somatic alterations in HRR pathway genes were detected in 32.1% young and 40.6% old BC patients. While similar frequencies of ERBB2 amplification (14.6% vs. 18.2%; P= 0.41) were detected in young and old BC patients, older patients carried more ERBB2 mutations (1.5% vs. 7.3%, P= 0.01). Interestingly, the highest rate of ERBB2 amplification was observed in the 20-30 years age group. Alterations in NF1 (10.6% vs. 3.6%, P=0.02) and PKHD1 (6.9% vs. 2.2%, P=0.04) were more frequent in older patients. Alterations in the PI3K pathway genes were more enriched in the older BC patients with overall mutational frequencies of 55.5% and 68.6% (P=0.01) in young and old subgroups, respectively. Finally, we observed an age-dependent increase in tumor mutational burden. Conclusion: BC in young and old patients exhibited different genomic characteristics that could be taken into consideration for treatment recommendations. Citation Format: Jiaqi Liu, Ziqi Jia, Gang Liu, Xiang Wang, Qi Meng, Sha Wang, Yang Shao. Differences in clinical actionability by comparing mutational landscape of young and old breast cancer patients [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 5772.