title: Genomic mutation-driven metastatic breast cancer therapy: a single center experience.
abstract: Next-Generation Sequencing (NGS) has made genomic mutation-driven therapy feasible for metastatic breast cancer (MBC) patients. We frequently submit tumor tissue from MBC patients for targeted NGS of tumor using the Illumina HiSeq 2000 platform (FoundationOne®, Foundation Medicine, MA). Herein, we report the results and clinical impact of this test in MBC patients.
  
  
  
  We identified patients with MBC treated at City of Hope from January 2014 to May 2016 who underwent NGS. Patients' clinical characteristics, response to treatment (clinical assessment of tumor regression), and genomic mutation profiles were reviewed.
  
  
  
  Forty-four patients with MBC underwent NGS: 24 triple negative breast cancer, 16 estrogen receptor positive, and 4 human epidermal growth factor receptor 2 positive patients. Twenty-three patients received more than three lines of chemotherapy prior to NGS. Actionable mutations (potentially responsive to targeted therapies that are on the market or in registered clinical trials) were identified in almost all patients (42/44; 95%) and over half of these 42 patients with actionable mutations (23/42; 55%) initiated mutation-driven targeted therapies. Of these 23 patients, 16/23 (70%) had assessable responses, and 7/23 (30%) were not assessable for response due to short exposure (<2 weeks) or hospice transition. The remaining 19/42 (45%) patients did not initiate targeted therapy.
  
  
  
  NGS can identify effective targeted therapy options for MBC patients based on actionable mutations that were not previously offered based on pathology type. NGS should be performed early in patients with good performance status and preferably in clinical settings where genomic mutation-driven therapeutic trials are available.
authors.affiliation: Department of Medical Oncology & Molecular Therapeutics, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Medical Oncology & Molecular Therapeutics, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Yost
authors.forename: John
authors.initials: J
authors.lastname: Yim
authors.affiliation: Bioinformatics Core Facility, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
authors.forename: Yate-Ching
authors.initials: YC
authors.lastname: Yuan
authors.affiliation: Department of Medical Oncology & Molecular Therapeutics, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Solomon
authors.affiliation: Department of Medical Oncology & Molecular Therapeutics, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
authors.forename: Isa
authors.initials: I
authors.lastname: Mambetsariev
authors.affiliation: Department of Medical Oncology & Molecular Therapeutics, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
authors.forename: Sumanta
authors.initials: S
authors.lastname: Pal
authors.affiliation: Department of Biostatistics, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.affiliation: Department of Medical Oncology & Molecular Therapeutics, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.affiliation: Department of Population Sciences, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.affiliation: Department of Medical Oncology & Molecular Therapeutics, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Mortimer
keywords: genomic mutation; genomic profiling; metastatic breast cancer (MBC); next-generation sequencing (NGS); targeted therapy