Abstract 6468: Prognostic genomic alterations associated with recurrence after primary therapy for patients with luminal B breast cancer
Purpose: Luminal type breast cancers account for the most common subtypes of breast cancers, among which luminal B subtype is relatively faster tumor growing and confers substantial risk of recurrence after primary treatment despite adjuvant endocrine therapy. Understanding the molecular alterations underlying the poorer survival outcome for luminal B tumors represents an unmet medical need. Experimental design: The archival samples of 16 recurrences within 5 years, 3 recurrences between 5 10 years and 24 non recurrence tumor tissues from luminal B breast cancer patients were retrieved. Genomic alterations of these 43 breast cancer samples were detected using deep next generation sequencing of a 440 gene panel. The mRNA levels of candidate genes in breast cancer patients were analyzed from The Cancer Genome Atlas (TCGA) database. Results: Overall, genomic alterations were found in 340 genes, including single nucleotide variants and copy number variation. Comparing to the non recurrence tumors, NUP98 (31.3% MAPK4 (18.8% PTEN (18.8% PER1 (18.8% and TRIP11 (18.8% showed higher population frequency in the recurrence tumors, and IGF2R (50.0% PIM1 (45.8% and ROS1 (37.5% were dominate in the non recurrence tumors. After a validation with the public clinical dataset, we identified three potential prognostic biomarkers, including NUP98, PER1, and TRIP11. We observed missense mutation or copy number deletion of NUP98, PER1 and TRIP11 in early recurrence tumors. Data from TCGA database exhibited patients with breast cancer harbored lower NUP98, PER1 and TRIP11 transcripts levels. Notably, lower NUP98, PER1 and TRIP11 expression levels correlated with worse recurrence free survival in luminal B breast cancer. Interestingly, based on algorithm for visualization of protein interaction network, we found these 3 genes were all involved in androgen receptor signaling network. Conclusion: Our study identified NUP98, PER1, and TRIP11 which potentially served as biomarkers to predict recurrence in luminal B breast cancer. Further research is required to understand the association between genomic alterations and androgen receptor signaling as well as its clinical impact. Citation Format: Chun Yu Liu, Ji Lin Chen, Yi Ting Yang, Yi Fang Tsai, Ta Chung Chao, Kien Thiam Tan, Wan Lun Wang, Pei Ju Lien, Shu Jen Chen, Ling Ming Tseng. Prognostic genomic alterations associated with recurrence after primary therapy for patients with luminal B breast cancer [abstract] In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27 28 and Jun 22 24. Philadelphia (PA) AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6468.