title: Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab.
abstract: BACKGROUND
  Central nervous system (CNS) disease as the site of first relapse after exposure to adjuvant trastuzumab has been reported. We carried out comprehensive meta-analysis to determine the risk of CNS metastases as the first site of recurrence in patients with HER2-positive breast cancer who received adjuvant trastuzumab.
  
  
  METHODS
  Eligible studies include randomized trials of adjuvant trastuzumab administered for 1 year to patients with HER2-positive breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the incidence, relative risk (RR), and 95% confidence intervals (CIs) using fixed-effects inverse variance and random-effects models.
  
  
  RESULTS
  A total of 9020 patients were included. The incidence of CNS metastases as first site of disease recurrence in HER2-positive patients receiving adjuvant trastuzumab was 2.56% (95% CI 2.07% to 3.01%) compared with 1.94% (95% CI 1.54% to 2.38%) in HER2-positive patients who did not receive adjuvant trastuzumab. The RR of the CNS as first site of relapse in trastuzumab-treated patients was 1.35 (95% CI 1.02-1.78, P = 0.038) compared with control arms without trastuzumab therapy. The ratio of CNS metastases to total number of recurrence events was 16.94% (95% CI 10.85% to 24.07%) and 8.33% (95% CI 6.49% to 10.86%) for the trastuzumab-treated and control groups, respectively. No statistically significant differences were found based on trastuzumab schedule or median follow-up time. No evidence of publication bias was observed.
  
  
  CONCLUSIONS
  Adjuvant trastuzumab is associated with a significant increased risk of CNS metastases as the site of first recurrence in HER2-positive breast cancer patients.
authors: Division of Medical Oncology, Department of Internal Medicine, Arthur G James Cancer Hospital and Richard J Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, USA. erin.olson@osumc.edu
authors: E M
authors: EM
authors: Olson
authors: M
authors: M
authors: Abdel-Rasoul
authors: J
authors: J
authors: Maly
authors: C S
authors: CS
authors: Wu
authors: N U
authors: NU
authors: Lin
authors: C L
authors: CL
authors: Shapiro
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D016543:Central Nervous System Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000556:secondary*; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced / Q000235:genetics / Q000556:secondary*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012307:Risk Factors; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: breast cancer; central nervous system; hER2; meta-analysis; metastases; trastuzumab