title: Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER.
abstract: OBJECTIVE
  registHER is a prospective, observational study of 1,023 newly diagnosed HER2-positive metastatic breast cancer (MBC) patients.
  
  
  METHODS
  Baseline characteristics of patients with and without central nervous system (CNS) metastases were compared; incidence, time to development, treatment, and survival after CNS metastases were assessed. Associations between treatment after CNS metastases and survival were evaluated.
  
  
  RESULTS
  Of the 1,012 patients who had confirmed HER2-positive tumors, 377 (37.3%) had CNS metastases. Compared with patients with no CNS metastases, those with CNS metastases were younger and more likely to have hormone receptor-negative disease and higher disease burden. Median time to CNS progression among patients without CNS disease at initial MBC diagnosis (n = 302) was 13.3 months. Treatment with trastuzumab, chemotherapy, or surgery after CNS diagnosis was each associated with a statistically significant improvement in median overall survival (OS) following diagnosis of CNS disease (unadjusted analysis: trastuzumab vs. no trastuzumab, 17.5 vs. 3.8 months; chemotherapy vs. no chemotherapy, 16.4 vs. 3.7 months; and surgery vs. no surgery, 20.3 vs. 11.3 months). Although treatment with radiotherapy seemed to prolong median OS (13.9 vs. 8.4 months), the difference was not significant (P = 0.134). Results of multivariable proportional hazards analyses confirmed the independent significant effects of trastuzumab and chemotherapy (HR = 0.33, P < 0.001; HR = 0.64, P = 0.002, respectively). The effects of surgery and radiotherapy did not reach statistical significance (P = 0.062 and P = 0.898, respectively).
  
  
  CONCLUSIONS
  For patients with HER2-positive MBC evaluated in registHER, the use of trastuzumab, chemotherapy, and surgery following CNS metastases were each associated with longer survival.
authors.affiliation: University of Pittsburgh Cancer Center, Pittsburgh, Pennsylvania 15213, USA. brufskyam@upmc.edu
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brufsky
authors.forename: Musa
authors.initials: M
authors.lastname: Mayer
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kaufman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tan-Chiu
authors.forename: Debu
authors.initials: D
authors.lastname: Tripathy
authors.forename: Iulia Cristina
authors.initials: IC
authors.lastname: Tudor
authors.forename: Lisa I
authors.initials: LI
authors.lastname: Wang
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Brammer
authors.forename: Mona
authors.initials: M
authors.lastname: Shing
authors.forename: Marianne Ulcickas
authors.initials: MU
authors.lastname: Yood
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016543:Central Nervous System Neoplasms / Q000453:epidemiology / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012042:Registries; D013997:Time Factors
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases