title: Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases.
abstract: BACKGROUND
  Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit.
  
  
  METHODS
  Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy.
  
  
  RESULTS
  Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone (P=0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P=0.012).
  
  
  CONCLUSIONS
  This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS ≥70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy.
authors: Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria.
authors: R
authors: R
authors: Bartsch
authors: A
authors: A
authors: Berghoff
authors: U
authors: U
authors: Pluschnig
authors: Z
authors: Z
authors: Bago-Horvath
authors: P
authors: P
authors: Dubsky
authors: A
authors: A
authors: Rottenfusser
authors: C
authors: C
authors: DeVries
authors: M
authors: M
authors: Rudas
authors: F
authors: F
authors: Fitzal
authors: K
authors: K
authors: Dieckmann
authors: R M
authors: RM
authors: Mader
authors: M
authors: M
authors: Gnant
authors: C C
authors: CC
authors: Zielinski
authors: G G
authors: GG
authors: Steger
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016019:Survival Analysis; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab