title: Central nervous system metastases in women after multimodality therapy for high risk breast cancer.
abstract: BACKGROUND
  Central nervous system (CNS) relapse is increasing in breast cancer. This increase may reflect altered failure patterns from adjuvant therapy, more effective systemic therapy with improved control in non-CNS sites, or a resistant breast cancer subtype.
  
  
  METHODS
  To determine the factors associated with clinical CNS relapse, we examined response to neoadjuvant chemotherapy (chemosensitivity), time to relapse and sites of relapse in a cohort of 140 patients without evidence of metastasis at presentation.
  
  
  RESULTS
  At 5 years (interquartile range 3-6 years), 44 (31%) patients developed distant metastases, including 13 with CNS metastases. CNS relapse was early (median 24 months after diagnosis) and associated with relapse in bone and liver, suggesting hematogenous dissemination. Those with CNS relapse were younger at diagnosis (40 versus 49 years) and more likely to have lymphovascular invasion in the primary tumor compared with non-CNS metastases. Response to neoadjuvant chemotherapy was not different (69% versus 73% response rate) between the two groups. Extent of residual disease after chemotherapy was strongly associated with relapse outside the CNS but not CNS relapses. The CNS was an isolated or dominant site of metastasis in 8 of 13. Despite treatment, most patients with CNS involvement died of neurologic causes a median of 6 months later.
  
  
  CONCLUSIONS
  Breast cancers that develop CNS metastases differ from those that develop metastases elsewhere. Both tumor behavior and reduced chemotherapy accessibility to the CNS may contribute to increased CNS involvement in breast cancer patients treated with multimodality therapy.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina, 3009 Old Clinic Building, Chapel Hill, NC, 27599-7305, USA. lisa_carey@med.unc.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Ewend
authors.forename: Richard
authors.initials: R
authors.lastname: Metzger
authors.forename: Lynda
authors.initials: L
authors.lastname: Sawyer
authors.forename: E Claire
authors.initials: EC
authors.lastname: Dees
authors.forename: Carolyn I
authors.initials: CI
authors.lastname: Sartor
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.forename: Mark L
authors.initials: ML
authors.lastname: Graham
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents