Abstract PO4-14-11: Findings of clinically significant variants (Tier IA) with OmniSeq INSIGHT ® in a breast cancer cohort of 987 patients
Authors: Ko Heidi , Dash Durga Prasad , Severson Eric , Strickland Kyle , Bliss Zachery , DePietro Paul , Conroy Jeffrey , Ramkissoon Shakti , Zhang Shengle 
Published: May 2024

Abstract
Background:
There were an estimated 2.3 million new breast cancer cases worldwide in 2020, with breast cancer now the most diagnosed type of cancer representing 25% of cancer cases and 17% of cancer deaths (1). The GLOBOCAN Cancer Tomorrow prediction tool estimates that incidence will increase by &gt; 45% by 2040 (2). Optimal treatment for breast cancer is increasingly dependent upon knowing a patient’s somatic and germline genomic alteration status. To highlight the importance of these genomic alterations, we provide an overview of the genomic findings in 987 consecutive breast cancer patients tested in the course of routine clinical care.
Methods:
Comprehensive Genomic and Immune Profiling (CGIP) was performed on 987 qualified breast cancer samples at a CAP/CLIA and NYS CLEP certified reference laboratory with the OmniSeq INSIGHT ® test (3). OmniSeq INSIGHT ® is a next generation sequencing-based laboratory developed test for the detection of genomic variants, signatures, HLA Class I genotypes, and immune gene expression in formalin-fixed paraffin-embedded (FFPE) tumor tissue. DNA is sequenced to detect small variants in the full exonic coding region of 523 genes, copy number alterations in 59 genes (gains and losses), as well as analysis of microsatellite instability (MSI) and tumor mutational burden (TMB). RNA is sequenced to detect fusions and splice variants in 55 genes, in addition to mRNA expression in 64 immune genes. The resultant information, along with PD-L1 protein expression by immunohistochemistry (IHC), is intended for use by qualified health care professionals in accordance with professional guidelines in oncology for management of patients with solid neoplasms. Tier IA variants include variants with strong clinical significance as per AMP–ASCO–CAP recommendations (4).
Results:
There were 384 Tier IA variants detected in 370 of 987 breast cancer patients (~37.5%) with 251 in PIK3CA (65.3%), 60 in ERBB2 (15.6%), 46 in BRCA2 (11.9%), 19 in BRCA1 (4.9%), 4 in NTRK3 (1.0%), 1 in NTRK1 (0.26%) and 1 in PALB2 (0.26%) including copy number variations (CNV), gene fusion and single nucleotide variants (SNV).
At the individual gene level for Tier IA variants, PIK3CA had 251 SNVs detected, ERBB2 had 55 CNVs, 1 gene fusion and 4 SNVs detected, BRCA2 had 39 SNVs and 8 CNVs detected, BRCA1 had 19 SNVs, NTRK3 had 4 gene fusions, NTRK1 had 1 gene fusion and PALB2 had 1 SNV detected.
At the variant class level, there were 63 CNVs, 6 gene fusions and 315 SNVs observed.
Conclusions:
CGIP for breast cancer patients identified one or more clinically significant Tier IA genomic alterations that directs targeted therapy in ~ 37.5% of patients in a cohort of real world patients tested during the standard course of clinical care. This highlights the need for comprehensive genomic testing in breast cancer patients to drive therapeutic decision making.
References:
1. Sung H et al.; Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries; CA Cancer J Clin, 2021 May;71(3):209-249.
2. Heer E et al.; Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study; Lancet Glob Health, 2020
3. Conroy JM et al.; A scalable high-throughput targeted next-generation sequencing assay for comprehensive genomic profiling of solid tumors; PLoS One. 2021
4. Li MM et al.; Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the association for molecular pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagnost. 2017;19(1):4–23.
Citation Format: Heidi Ko, Durga Prasad Dash, Eric Severson, Kyle Strickland, Zachery Bliss, Paul DePietro, Jeffrey Conroy, Shakti Ramkissoon, Shengle Zhang. Findings of clinically significant variants (Tier IA) with OmniSeq INSIGHT ® in a breast cancer cohort of 987 patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-14-11.