title: Changing molecular profile of brain metastases compared with matched breast primary cancers and impact on clinical outcomes.
abstract: BACKGROUND
  Breast cancer commonly metastasises to the brain, but little is known about changes in the molecular profile of the brain secondaries and impact on clinical outcomes.
  
  
  METHODS
  Patients with samples from brain metastases and matched breast cancers were included. Immunohistochemical analysis for oestrogen receptor, progesterone receptor, p27kip1, cyclin D1, epidermal growth factor receptor, insulin like growth factor 1, insulin like growth factor 1 receptor, vascular endothelial growth factor A, transforming growth factor-β and HER2 receptor was performed. Borderline HER2 results were analysed by fluorescent in situ hybridisation. Levels of expression were compared, with review of effect on clinical outcomes.
  
  
  RESULTS
  A total of 41 patients were included. Of the patients, 20% had a change in oestrogen receptor or HER2 in their brain metastasis that could affect therapeutic decisions. There were statistically significant rises in brain metastases for p27kip1 (P=0.023) and cyclin D1 (P=0.030) and a fall in vascular endothelial growth factor A (P=0.012). Overall survival from the time of metastasis increased significantly with oestrogen receptor-positive (P=0.005) and progesterone receptor-positive (P=0.013) brain lesions and with a longer duration from diagnosis of the breast primary (P<0.001).
  
  
  CONCLUSIONS
  In this cohort there were phenotypic differences in metastatic brain tumours compared with matched primary breast tumours. These could be relevant for aetiology, and have an impact on prognostication, current and future therapies.
authors.affiliation: Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, TR1 3LJ, UK.
authors.forename: A H
authors.initials: AH
authors.lastname: Thomson
authors.affiliation: Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, TR1 3LJ, UK.
authors.forename: J
authors.initials: J
authors.lastname: McGrane
authors.affiliation: Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, TR1 3LJ, UK.
authors.forename: J
authors.initials: J
authors.lastname: Mathew
authors.affiliation: Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, TR1 3LJ, UK.
authors.forename: J
authors.initials: J
authors.lastname: Palmer
authors.affiliation: Derriford Hospital, Derriford Road, Crownhill, Plymouth, Devon, PL6 8DH, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Hilton
authors.affiliation: Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, TR1 3LJ, UK.
authors.forename: G
authors.initials: G
authors.lastname: Purvis
authors.affiliation: Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, TR1 3LJ, UK.
authors.forename: R
authors.initials: R
authors.lastname: Jenkins
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; 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; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human