title: Individualized Molecular Analyses Guide Efforts (IMAGE): A Prospective Study of Molecular Profiling of Tissue and Blood in Metastatic Triple-Negative Breast Cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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. Clin Cancer Res; 23(2); 379-86. ©2016 AACR.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Parsons
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Beaver
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ashley
authors.initials: A
authors.lastname: Cimino-Mathews
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Axilbund
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Chu
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Roisin M
authors.initials: RM
authors.lastname: Connolly
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Rory L
authors.initials: RL
authors.lastname: Cochran
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Croessmann
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Travis A
authors.initials: TA
authors.lastname: Clark
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Gocke
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Stacie C
authors.initials: SC
authors.lastname: Jeter
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Kennedy
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Josh
authors.initials: J
authors.lastname: Lauring
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Justin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Doron
authors.initials: D
authors.lastname: Lipson
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Geoff A
authors.initials: GA
authors.lastname: Otto
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Rosner
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Shannon
authors.initials: S
authors.lastname: Slater
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Dustin A
authors.initials: DA
authors.lastname: VanDenBerg
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Young
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Zabransky
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jane
authors.initials: J
authors.lastname: Zorzi
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. bpark2@jhmi.edu vstearn1@jhmi.edu.
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. bpark2@jhmi.edu vstearn1@jhmi.edu.
authors.forename: Ben H
authors.initials: BH
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001706:Biopsy; D004273:DNA, Neoplasm / Q000097:blood*; D004358:Drug Therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D057285:Precision Medicine; D064726:Triple Negative Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins