title: Retrospective analysis of risk factors for central nervous system metastases in operable breast cancer: effects of biologic subtype and Ki67 overexpression on survival.
abstract: OBJECTIVE
  Identifying factors that predispose patients to central nervous system (CNS) metastases may hasten disease detection and improve treatment outcomes.
  
  
  METHODS
  We reviewed the records of patients who were diagnosed with clinical stage I-III primary breast cancer at the National Cancer Center Hospital East from 2003 to 2005. Cox proportional hazard models were fitted to reveal risk factors for CNS metastases.
  
  
  RESULTS
  The median follow-up period after the operation was 53.5 months. Among the 591 identified patients with breast cancer, 76 experienced a relapse. Seventeen patients developed CNS metastases. Multivariate analysis indicated that the triple negative (TN) subtype (hazard ratio = 5.5) and a high Ki67 labeling index (LI; hazard ratio = 3.9) were associated with a higher risk for CNS metastases. At 4 years, the TN subtype was associated with significantly worse overall and disease-free survival rates and a higher cumulative incidence of CNS metastases compared with hormone receptor-positive/ human epidermal growth factor receptor-2-negative tumors. Breast cancers with a Ki67 LI ≥30% were also associated with lower overall and disease-free survival rates and a higher cumulative incidence of CNS metastases compared with cancers with a Ki67 LI <30%.
  
  
  CONCLUSIONS
  TN or Ki67-overexpressing breast cancer produced earlier CNS metastases and lower disease-free and overall survival rates.
authors.affiliation: Divisions of Oncology/Hematology, National Cancer Center Hospital East, Kashiwa, Japan. mishihara @ clin.medic.mie-u.ac.jp
authors.forename: Mikiya
authors.initials: M
authors.lastname: Ishihara
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mukai
authors.forename: Shunji
authors.initials: S
authors.lastname: Nagai
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Onozawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Nihei
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimada
authors.forename: Noriaki
authors.initials: N
authors.lastname: Wada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D019394:Ki-67 Antigen / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone