title: Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab.
abstract: OBJECTIVE
  The aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab.
  
  
  METHODS
  Medical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively.
  
  
  RESULTS
  Median follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER- and PR-) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33-8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33-8.71) were significant risk factors for development of brain metastasis as the first site of recurrence.
  
  
  CONCLUSIONS
  In patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER- and PR-) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey. Electronic address: tonyalionder@yahoo.com.
authors.forename: Onder
authors.initials: O
authors.lastname: Tonyali
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Ugur
authors.initials: U
authors.lastname: Coskun
authors.affiliation: Department of Medical Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey.
authors.forename: Sinemis
authors.initials: S
authors.lastname: Yuksel
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
authors.forename: Mevlude
authors.initials: M
authors.lastname: Inanc
authors.affiliation: Department of Medical Oncology, Ankara Oncology Training and Research Hospital, Ankara, Turkey.
authors.forename: Oznur
authors.initials: O
authors.lastname: Bal
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Tulay
authors.initials: T
authors.lastname: Akman
authors.affiliation: Department of Medical Oncology, Konya Numune Education and Research Hospital, Konya, Turkey.
authors.forename: Dogan
authors.initials: D
authors.lastname: Yazilitas
authors.affiliation: Department of Medical Oncology, Ali Osman Sonmez Oncology Hospital, Bursa, Turkey.
authors.forename: Arife
authors.initials: A
authors.lastname: Ulas
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Dicle University, Diyarbakir, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kucukoner
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Inonu University, Malatya, Turkey.
authors.forename: Asude
authors.initials: A
authors.lastname: Aksoy
authors.affiliation: Department of Medical Oncology, Ankara Ataturk Education and Research Hospital, Ankara, Turkey.
authors.forename: Umut
authors.initials: U
authors.lastname: Demirci
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Afyon Kocatepe University Faculty of Medicine, Afyonkarahisar, Turkey.
authors.forename: Mukremin
authors.initials: M
authors.lastname: Uysal
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Mugla University, Mugla, Turkey.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Tanriverdi
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Gunaydin
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey.
authors.forename: Ahmet Taner
authors.initials: AT
authors.lastname: Sumbul
authors.affiliation: Department of Medical Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Yildiz
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
authors.forename: Halit
authors.initials: H
authors.lastname: Karaca
authors.affiliation: Department of Medical Oncology, Ankara Oncology Training and Research Hospital, Ankara, Turkey.
authors.forename: Berna
authors.initials: B
authors.lastname: Oksuzoglu
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Aydin
authors.initials: A
authors.lastname: Ciltas
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Suleyman
authors.initials: S
authors.lastname: Buyukberber
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Benekli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000453:epidemiology / Q000556:secondary*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008408:Mastectomy; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D000068878:Trastuzumab / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Adjuvant therapy; Brain metastasis; Breast cancer; Trastuzumab