title: Brain metastases free survival differs between breast cancer subtypes.
abstract: BACKGROUND
  Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010.
  
  
  METHODS
  Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test.
  
  
  RESULTS
  Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34-16.66) compared with 18 months (95% CI: 14.46-21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71-44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014).
  
  
  CONCLUSIONS
  Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes.
authors.affiliation: Comprehensive Cancer Center Vienna, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Berghoff
authors.forename: Z
authors.initials: Z
authors.lastname: Bago-Horvath
authors.forename: C
authors.initials: C
authors.lastname: De Vries
authors.forename: P
authors.initials: P
authors.lastname: Dubsky
authors.forename: U
authors.initials: U
authors.lastname: Pluschnig
authors.forename: M
authors.initials: M
authors.lastname: Rudas
authors.forename: A
authors.initials: A
authors.lastname: Rottenfusser
authors.forename: M
authors.initials: M
authors.lastname: Knauer
authors.forename: H
authors.initials: H
authors.lastname: Eiter
authors.forename: F
authors.initials: F
authors.lastname: Fitzal
authors.forename: K
authors.initials: K
authors.lastname: Dieckmann
authors.forename: R M
authors.initials: RM
authors.lastname: Mader
authors.forename: M
authors.initials: M
authors.lastname: Gnant
authors.forename: C C
authors.initials: CC
authors.lastname: Zielinski
authors.forename: G G
authors.initials: GG
authors.lastname: Steger
authors.forename: M
authors.initials: M
authors.lastname: Preusser
authors.forename: R
authors.initials: R
authors.lastname: Bartsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone