Title |
Individualized Molecular Analyses Guide Efforts (IMAGE): A Prospective Study of Molecular Profiling of Tissue and Blood in Metastatic Triple-Negative Breast Cancer
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Published in |
Clinical Cancer Research, January 2017
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DOI | 10.1158/1078-0432.ccr-16-1543 |
Pubmed ID | |
Authors |
Heather A. Parsons, Julia A. Beaver, Ashley Cimino-Mathews, Siraj M. Ali, Jennifer Axilbund, David Chu, Roisin M. Connolly, Rory L. Cochran, Sarah Croessmann, Travis A. Clark, Christopher D. Gocke, Stacie C. Jeter, Mark R. Kennedy, Josh Lauring, Justin Lee, Doron Lipson, Vincent A. Miller, Geoff A. Otto, Gary L. Rosner, Jeffrey S. Ross, Shannon Slater, Philip J. Stephens, Dustin A. VanDenBerg, Antonio C. Wolff, Lauren E. Young, Daniel J. Zabransky, Zhe Zhang, Jane Zorzi, Vered Stearns, Ben H. Park |
Abstract |
The clinical utility of next generation sequencing (NGS) in breast cancer has not been demonstrated.We hypothesized we could perform NGS of a new biopsy from patients with metastatic triple negative breast cancer (TNBC) in a clinically actionable timeframe. We planned to enroll 40 patients onto a prospective study, Individualized Molecular Analyses Guide Efforts (IMAGE),to evaluate the feasibility of obtaining a new biopsy of a metastatic site, perform NGS (FoundationOne{trade mark, serif}), and convene a molecular tumor board to formulate treatment recommendations within 28 days. We collected blood at baseline and at time of restaging to assess cell-free circulating plasma tumor DNA (ptDNA). We enrolled 26 women with metastatic TNBC who had received {greater than or equal to}1 line of prior chemotherapy, and 20 (77%) underwent NGS of a metastatic site biopsy.Twelve(60%) evaluable patients received treatment recommendations within 28 days of consent. The study closed after 20 patients underwent NGS, based on protocol-specified interim futility analysis.Three patients went on to receive genomically directed therapies. Twenty-four of 26 patients had genetic alterations successfully detected in ptDNA. Among 5 patients, 4 mutations found in tumor tissues were not identified in blood and 4 mutations found in blood were not found in corresponding tumors.In nine patients, NGS of follow up blood samples showed 100% concordance with baseline blood samples. This study demonstrates challenges of performing NGS on prospective tissue biopsies in patients with metastatic TNBC within 28 days, while also highlighting the potential use of blood as a more time efficient and less invasive method of mutational assessment. |
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Other | 12 | 13% |
Student > Master | 12 | 13% |
Student > Ph. D. Student | 8 | 9% |
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Other | 16 | 18% |
Unknown | 19 | 21% |
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Pharmacology, Toxicology and Pharmaceutical Science | 3 | 3% |
Other | 10 | 11% |
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