title: Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer.
abstract: BACKGROUND
  The purpose of this study was to compare the expression and the prognostic effect of the breast cancer stem cell marker aldehyde dehydrogenase-1 (ALDH1) in young and elderly breast cancer patients.
  
  
  METHODS
  The study population (N = 574) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Median follow-up was 17.9 years (range: 0.1 to 23.5). Tissue microarray slides were immunohistochemically stained for ALDH1 expression and quantified by two independent observers who were blinded to clinical outcome. Assessment of the prognostic effect of ALDH1 expression was stratified according to age and systemic treatment.
  
  
  RESULTS
  Complete lack of expression of ALDH1 was found in 40% of tumors. With increasing age more tumors showed complete absence of ALDH1 expression (P < .001). In patients aged > 65 years, ALDH1 status was not associated with any clinical outcome. Conversely, in patients aged < 65 years, ALDH1 positivity was an independent risk factor of worse outcome for relapse free period (hazard ratio = 1.71 (95% CI, 1.09 to 2.68); P = .021) and relative survival (relative excess risks of death = 2.36 (95% CI, 1.22 to 3.68); P = .016). Ten-year relative survival risk was 57% in ALDH1-positive patients compared to 83% in ALDH1-negative patients.
  
  
  CONCLUSIONS
  ALDH1 expression and its prognostic effect are age-dependent. Our results support the hypothesis that breast cancer biology is different in elderly patients compared to their younger counterparts and emphasizes the importance of taking into consideration age-specific interactions in breast cancer research.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J Sven D
authors.initials: JS
authors.lastname: Mieog
authors.forename: Esther M
authors.initials: EM
authors.lastname: de Kruijf
authors.forename: Esther
authors.initials: E
authors.lastname: Bastiaannet
authors.forename: Peter Jk
authors.initials: PJ
authors.lastname: Kuppen
authors.forename: Anita
authors.initials: A
authors.lastname: Sajet
authors.forename: Anton Jm
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Vincent Thbm
authors.initials: VT
authors.lastname: Smit
authors.forename: Cornelis Jh
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: Liefers
mesh_terms: D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D011379:Prognosis; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase