Individualized Molecular Analyses Guide Efforts (IMAGE): A prospective study of molecular profiling of tissue and blood in metastatic triple-negative breast cancer

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. RossShannon 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

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The clinical utility of next-generation sequencing (NGS) in breast cancer has not been demonstrated. We hypothesized that we could perform NGS of a new biopsy from patients with metastatic triple-negative breast cancer (TNBC) in a clinically actionable timeframe. Experimental Design: 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), 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). Results: We enrolled 26 women with metastatic TNBC who had received ≥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 9 patients, NGS of follow-up blood samples showed 100% concordance with baseline blood samples. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)379-386
Number of pages8
JournalClinical Cancer Research
Volume23
Issue number2
DOIs
StatePublished - Jan 15 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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