title: Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.
abstract: BACKGROUND
  Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.
  
  
  METHODS
  We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis.
  
  
  RESULTS
  Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years.
  
  
  CONCLUSIONS
  Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ; School of Medicine, National Yang-Ming University, Taipei, Taiwan ; Program in Molecular Medicine, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Man-Hsin
authors.initials: MH
authors.lastname: Hung
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ; School of Medicine, National Yang-Ming University, Taipei, Taiwan ; Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan ; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Cheng-Ying
authors.initials: CY
authors.lastname: Shiau
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan ; Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chin-Yi
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan ; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Tsai
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ling-Chen
authors.initials: LC
authors.lastname: Tai
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan ; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kuang-Liang
authors.initials: KL
authors.lastname: King
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ta-Chung
authors.initials: TC
authors.lastname: Chao
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jen-Hwey
authors.initials: JH
authors.lastname: Chiu
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan ; Division of General Surgery, Department of Surgery, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Cheng-Hsi
authors.initials: CH
authors.lastname: Su
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan ; National Yang-Ming University Hospital, I-Lan, Taiwan.
authors.forename: Su-Shun
authors.initials: SS
authors.lastname: Lo
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Cheng-Hwai
authors.initials: CH
authors.lastname: Tzeng
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan ; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Shyr
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan ; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ling-Ming
authors.initials: LM
authors.lastname: Tseng
mesh_terms: D000328:Adult; D000367:Age Factors; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012306:Risk; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone