title: Multifactorial central nervous system recurrence susceptibility in patients with HER2-positive breast cancer: epidemiological and clinical data from a population-based cancer registry study.
abstract: BACKGROUND
  A series of retrospective studies have reported that patients with human epidermal growth factor receptor 2(HER2)-positive breast cancer are at a greater risk of central nervous system (CNS) metastases. Trastuzumab, which does not cross the blood-brain barrier, has been associated with this increased risk.
  
  
  METHODS
  The authors evaluated incidence, survival, and risk factors for CNS metastases in the incident breast cancer population systematically collected by the Parma Province Cancer Registry over the 4-year period between 2004 and 2007.
  
  
  RESULTS
  A total of 1458 patients with a diagnosis of stage I to III invasive breast cancer were analyzed for study purposes. At a median follow-up of 4.1 years, CNS events were observed in 1.3% and 5% of HER2-negative patients and HER2-positive patients, respectively (P < .0001). The administration of trastuzumab either as adjuvant therapy or for metastatic disease was associated with a significantly increased risk of CNS involvement at first disease recurrence and after first extracranial recurrence, respectively. According to multivariate analysis, HER2-positive status and trastuzumab treatment, high Ki-67 index, and hormone receptor negativity remained independent risk factors for the development of CNS metastasis.
  
  
  CONCLUSIONS
  To the authors' knowledge, this is the first population-based cancer registry study analyzing factors associated with CNS recurrence in a general population of newly diagnosed breast cancer patients with known HER2 status. The data from the current study provide evidence that patients with HER2-positive breast cancer have a significantly higher incidence of CNS metastasis after treatment with trastuzumab. Improvements in systemic control and overall survival associated with trastuzumab-based therapy may lead to an "unmasking" of CNS disease recurrence that would otherwise remain clinically silent before a patient's death.
authors.affiliation: Medical Oncology Unit and Cancer Registry of Parma Province, University Hospital of Parma, Parma, Italy. antoninomusolino@hotmail.com
authors.forename: Antonino
authors.initials: A
authors.lastname: Musolino
authors.forename: Laura
authors.initials: L
authors.lastname: Ciccolallo
authors.forename: Michele
authors.initials: M
authors.lastname: Panebianco
authors.forename: Elisa
authors.initials: E
authors.lastname: Fontana
authors.forename: Daniele
authors.initials: D
authors.lastname: Zanoni
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bozzetti
authors.forename: Maria
authors.initials: M
authors.lastname: Michiara
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Silini
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000453:epidemiology / Q000556:secondary*; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D011159:Population Surveillance; D011379:Prognosis; D012008:Recurrence; D012042:Registries; D012307:Risk Factors; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068878:Trastuzumab