Abstract 1122: Personalized oncogenomics in advanced stage breast cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 75; no. 15_Supplement; p. 1122
• Main Authors: Sun, Sophie, Gelmon, Karen A., Chia, Stephen, Lohrisch, Caroline, Shenkier, Tamara, Villa, Diego, Shen, Yaoqing, Jones, Martin, Pleasance, Erin, Kasaian, Katayoon, Eirew, Peter, Leelakumari, Sreeja, Ma, Yusanne, Ng, Tony, Yip, Stephen, Jones, Steven JM, Marra, Marco A., Laskin, Janessa J.
• Format: Journal Article
• Language: English
• Published: 01-08-2015
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-1122

Abstract
Background
Breast cancer is a complex disease with clinical, pathological, and molecular heterogeneity. Recent studies have identified several subtypes of breast cancers driven by specific molecular pathways that can be inhibited by targeted drugs. We studied the feasibility of using molecular data from whole genome and transcriptome sequencing of breast cancers to guide treatment.
Methods
Patients were consented as part of the Personalized Onco-Genomics (POG) study at the British Columbia Cancer Agency. Fresh tumor, blood for normal DNA, and archival tumor were collected. Tissue and blood samples were sequenced using the Ion Torrent AmpliSeq panel, followed by comprehensive DNA and RNA sequencing. In-depth bioinformatic analyses were performed. Somatic mutations, copy number changes, structural variants and gene expression were characterized. Results from genomic analyses were reviewed in a multi-disciplinary team.
Results
From August 2012 to October 2014, tissue samples from 30 patients with advanced stage breast cancer were analyzed. The median age at diagnosis was 53 years (range 32-75). The median number of lines of cytotoxic therapy prior to sequencing was 2 (range 0-10). All cases were invasive ductal carcinoma; 63% were ER+ and HER2-; 27% triple negative; 7% ER+ and HER2+; and 3% ER- and HER2+. The most frequently mutated genes were TP53 (67%), PI3KCA (23%), ESR1 (20%), ATM (10%), ARID1A (10%), and BRCA1/2 (10%). Somatic mutations in other genes of interest including HER2, PARP1, NF1, BAP1, PTEN, NOTCH1, were also identified. Molecular data were informative for patient care and/or actionable to guide treatment in 57% (17/30) of cases.
Conclusion
The use of whole genome sequencing technology to identify valuable molecular information to guide personalized breast cancer treatment is feasible. Further studies are warranted to evaluate the usefulness of genome-wide sequencing of breast cancers in clinical practice.
Citation Format: Sophie Sun, Karen A. Gelmon, Stephen Chia, Caroline Lohrisch, Tamara Shenkier, Diego Villa, Yaoqing Shen, Martin Jones, Erin Pleasance, Katayoon Kasaian, Peter Eirew, Sreeja Leelakumari, Yusanne Ma, Tony Ng, Stephen Yip, Steven JM Jones, Marco A. Marra, Janessa J. Laskin. Personalized oncogenomics in advanced stage breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1122. doi:10.1158/1538-7445.AM2015-1122