Abstract P6-10-26: Identification of copy number variation associated with lymph node metastasis in triple negative breast cancer
Authors: Pariyar Mamta , Mathe Andrea , Scott Rodney , Avery-Kiejda Kelly 
Published: March 2020

Abstract
Background: Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer which lacks receptors for-estrogen, progesterone and human epidermal growth factor 2. It accounts for approximately 10-20% of all breast cancer cases. It is commonly diagnosed in younger African-American women less than 40 years. There are no targeted therapies for this breast cancer subtype, therefore, chemotherapy and surgery remain the only options for treatment. However, there is a high chance of recurrence within three years of diagnosis and the majority of deaths occurs within the five years of diagnosis. High genomic aberration is a common event in this cancer where the differentially expressed genes in TNBC could be due to the variations in copy number of those genes. The dissemination of primary cancer cells to the lymphatic system represents one of the first signs of meta-static spread. In TNBC, any LN involvement is associated with worse disease-free and overall survival. Therefore, identification of copy number variations (CNVs) within LN metastases in this highly aggressive breast cancer subtype may serve as an indicator of prognosis. Objectives: The aim of the current study was to define regions of copy number gain or loss that are associated with metastasis to the lymph node in TNBC and their association with gene expression. Methods: Partek Genomic Suite was used to analyse the copy number variations in the study cohort containing 23 invasive ductal carcinoma (IDC), 12 lymph node metastasis (LNmets) and 3 normal adjacent tissues (NAT); as well as in validation cohort containing 70 IDC samples (Avery-Kiejda KA, Genom Data.2017;14:1-4).All the breast cancer samples were TNBC. The genomic segmentation algorithm was used for copy number detection. Moreover, their association with gene expression was also analysed using previous gene expression datasets (Accession No.GSE78758). Additionally, GO-enrichment and pathway analysis was performed to identify functional groups and pathways affected by copy number changes. Results: More CNV regions were amplified compared to loss in both the study and the validation cohort. The whole genome copy number profile was similar between IDC and lymph node metastases with 81% (263 in total) of amplified CNVs present in LNmets also present in matched IDCs, implying that many of the alterations in the primary tumour were carried over in metastasis. Very few genes were deleted and of those that were, only 2 were common to IDCs and LNmets. No significant CNVs were observed in NAT. Frequent amplification was mainly observed in chromosome 1q, 8q and 10p whereas the deletion in 4q, 5q and 14q was common in both IDC and metastasis samples. In total, 95 genes (66 gains and 29 losses) were only present in LNmet and not in IDCs from either the study or validation cohorts. According to GO-enrichment analysis, these LNmet associated genes were mainly enriched for DNA-binding transcription activity, cell fate specification and negative regulation of EGFR signalling pathway. Conclusion: This study has identified several regions of CNV in a well-defined TNBC cohort that could play major role in metastasis to lymph node.
Citation Format: Mamta Pariyar, Andrea Mathe, Rodney Scott, Kelly Avery-Kiejda. Identification of copy number variation associated with lymph node metastasis in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-26.