title: αB-crystallin Expression in Breast Cancer is Associated with Brain Metastasis.
abstract: OBJECTIVE
  The molecular chaperone αB-crystallin is expressed in estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 "triple-negative" breast carcinomas and promotes brain and lung metastasis. We examined αB-crystallin expression in primary breast carcinomas with metastatic data to evaluate its association with prognosis and site-specific metastases.
  
  
  METHODS
  αB-crystallin gene (CRYAB) expression was examined using publically available global-gene expression data (n=855 breast tumors) with first site of distant metastasis information ("855Met"). αB-crystallin protein expression was determined by immunohistochemistry using the clinically annotated tissue microarray (n=3987 breast tumors) from British Columbia Cancer Agency (BCCA). Kaplan-Meier and multivariable Cox regression analyses were used to evaluate the prognostic value of αB-crystallin. Multivariable logistic regression analysis was used to evaluate risks of αB-crystallin and other markers for site of metastasis.
  
  
  RESULTS
  In the 855Met dataset, αB-crystallin gene (CRYAB)expression was an independent predictor of brain as the first distant site of relapse (HR = 1.2, (95% CI 1.0-1.4),P= 0.021). In the BCCA series, αB-crystallin protein expression was an independent prognostic marker of poor breast cancer specific survival (HR = 1.3, (95% CI 1.1-1.6),P= 0.014). Among patients with metastases, αB-crystallin was the strongest independent predictor of brain metastasis (OR = 2.99 (95% CI 1.83-4.89),P< 0.0001) and the only independent predictor of brain as the first site of distant metastasis (OR = 3.15 (95% CI1.43-6.95),P= 0.005). αB-crystallin was also associated with worse survival (3.0 versus 4.7 months,P= 0.007).
  
  
  CONCLUSIONS
  αB-crystallin is a promising biomarker to identify breast cancer patients at high risk for early relapse in the brain, independent of ER and HER2 status.
authors.affiliation: Department of Radiation Oncology, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada.
authors.forename: K David
authors.initials: KD
authors.lastname: Voduc
authors.affiliation: Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Department of Pathology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: J Chuck
authors.initials: JC
authors.lastname: Harrell
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Hagen
authors.initials: H
authors.lastname: Kennecke
authors.affiliation: Department of Radiation Oncology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA.
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Minn
authors.affiliation: Department of Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Cryns
authors.affiliation: Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK.
authors.forename: Maggie C U
authors.initials: MCU
authors.lastname: Cheang
keywords: biomarker; brain; metastasis; tissue microarray; triple-negative breast cancer; αB-crystallin