title: Systematic analysis of early phase clinical studies for patients with breast cancer: Inclusion of patients with brain metastasis.
abstract: OBJECTIVE
  This systematic review aims to better define the limitations and patterns with which patients with MBC and CNS metastasis are enrolled into early phase developmental therapeutics trials.
  
  
  METHODS
  In June 2016, PubMed search was conducted using the following keywords: "Breast cancer". Drug-development phase 1, phase 2 or phase 1/2 trials for patients with MBC were included. Multiple-histology trials and trials without an efficacy endpoint were excluded.
  
  
  RESULTS
  In total, 1474 studies were included; Inclusion criteria for 423 (29%) allowed for CNS metastasis, 770 (52%) either excluded or did not document eligibility of patients with CNS disease. Trials accruing patients with HER2-positive MBC and including targeted therapies had higher odds of allowing for patients with CNS disease (adjusted OR 1.56, 95% CI 1.08-2.2.6; p=0.019 and 1.49, 95% 1.08-2.06; p=0.014, respectively). There were also higher odds of accrual of patients with CNS involvement into clinical trials over time (odds ratio=1.10, 95% CI 1.07-1.12; p<0.0001).
  
  
  CONCLUSIONS
  Most published early phase clinical trials either did not clearly document or did not allow for accrual of patients with CNS disease. Early phase trials with targeted agents or enrolling HER2+ MBC had higher odds of permitting CNS metastases.
authors.affiliation: Developmental Therapeutics Program, Division of Hematology Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United States. Electronic address: ricardo.costa@northwestern.edu.
authors.forename: R
authors.initials: R
authors.lastname: Costa
authors.affiliation: Department of Molecular and Cell Biology, University of Illinois at Urbana-Champaign, Urbana, IL, United States.
authors.forename: N
authors.initials: N
authors.lastname: Gill
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United States; Northwestern University Department of Preventive Medicine, Chicago, IL, United States.
authors.forename: A W
authors.initials: AW
authors.lastname: Rademaker
authors.affiliation: Developmental Therapeutics Program, Division of Hematology Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United States.
authors.forename: B A
authors.initials: BA
authors.lastname: Carneiro
authors.affiliation: Developmental Therapeutics Program, Division of Hematology Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United States.
authors.forename: Y K
authors.initials: YK
authors.lastname: Chae
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United States; Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
authors.forename: P
authors.initials: P
authors.lastname: Kumthekar
authors.affiliation: Developmental Therapeutics Program, Division of Hematology Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: W J
authors.initials: WJ
authors.lastname: Gradishar
authors.affiliation: Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA, United States.
authors.forename: R
authors.initials: R
authors.lastname: Kurzrock
authors.affiliation: Developmental Therapeutics Program, Division of Hematology Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United States.
authors.forename: F J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D001932:Brain Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000628:therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D018579:Patient Selection; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Brain metastasis; Breast cancer; Early phase clinical trials