title: Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death.
abstract: BACKGROUND
  To access the prognostic significance of HER-2 overexpression, the effect of trastuzumab and the cause of death in patients with brain metastases (BM) from breast cancer (BC).
  
  
  METHODS
  We analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy (WBRT) (without surgery or radiosurgery) between January 1998 and April 2006. Demographic data, tumor characteristics, and treatments were prospectively recorded. The impact of HER-2 overexpression and trastuzumab-based therapy on overall survival (OS) and the cause of death were evaluated.
  
  
  RESULTS
  The median follow-up for the whole population was 6.25 months (mean: 9.15; range: 0.23-53). The median survival time and 1-year survival rates after BM diagnosis were 7.43 months and 35.8% (95% CI: 28-45.7) respectively. The median survival time for HER-2 negative patients (n = 78), HER-2 positive patients not treated with trastuzumab (n = 20) and HER-2 positive patients treated with trastuzumab (n = 32) were 5.9 months, 5.6 months and 19.53 months, respectively. The 1-year survival rates were 26.1%, 29.2% and 62.6% respectively, (p < 0.004). Among the 18 HER-2 positive patients treated with trastuzumab who died, 11 (61%) apparently succumbed from CNS progression, in the face of stable or responsive non-CNS disease. Trastuzumab-based therapy was associated with a 51% reduction in the risk of death (multiadjusted hazard ratio: 0.49; 95% CI, 0.29-0.83).
  
  
  CONCLUSIONS
  In our experience, trastuzumab-based therapy for HER-overexpressing tumors was associated with improved survival in BM BC patients. This subgroup of patients may benefit from innovative approaches, in order to obtain better intra cerebral control.
authors.affiliation: Department of Radiation Oncology, Centre Hospitalier Privé Saint Grégoire, Saint Grégoire, France. rlescodan@vivalto-sante.com
authors.forename: Romuald
authors.initials: R
authors.lastname: Le Scodan
authors.forename: Ludivine
authors.initials: L
authors.lastname: Jouanneau
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.forename: Maya
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Youlia
authors.initials: Y
authors.lastname: Kirova
authors.forename: Pascal
authors.initials: P
authors.lastname: Cherel
authors.forename: Julie
authors.initials: J
authors.lastname: Gachet
authors.forename: Alain
authors.initials: A
authors.lastname: Labib
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mouret-Fourme
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002423:Cause of Death; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab