Individualized Molecular Analyses Guide Efforts (IMAGE): A Prospective Study of Molecular Profiling of Tissue and Blood in Metastatic Triple-Negative Breast Cancer

作者：Parsons Heather A; Beaver Julia A; Cimino Mathews Ashley; Ali Siraj M; Axilbund Jennifer; Chu David; Connolly Roisin M; Cochran Rory L; Croessmann Sarah; Clark Travis A; Gocke Christopher D; Jeter Stacie C; Kennedy Mark R; Lauring Josh; Lee Justin; Lipson Doron; Miller Vincent A; Otto Geoff A; Rosner Gary L; Ross Jeffrey S; Slater Shannon; Stephens Philip J; VanDenBerg Dustin A; Wolff Antonio C; Young Lauren E; Zabransky Daniel J; Zhang Zhe

来源：Clinical Cancer Research, 2017, 23(2): 379-386.

DOI：10.1158/1078-0432.CCR-16-1543

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 tumorDNA(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.

• 出版日期2017-1