title: Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study.
abstract: BACKGROUND
  Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood.
  
  
  METHODS
  We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women.
  
  
  RESULTS
  HRT use in patients with estrogen receptor (ER) protein positive tumors (n = 72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen.
  
  
  CONCLUSIONS
  Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Per.Hall@ki.se
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploner
authors.forename: Judith
authors.initials: J
authors.lastname: Bjöhle
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.forename: Chin-Yo
authors.initials: CY
authors.lastname: Lin
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
authors.forename: Lance D
authors.initials: LD
authors.lastname: Miller
authors.forename: Hans
authors.initials: H
authors.lastname: Nordgren
authors.forename: Yudi
authors.initials: Y
authors.lastname: Pawitan
authors.forename: Peter
authors.initials: P
authors.lastname: Shaw
authors.forename: Lambert
authors.initials: L
authors.lastname: Skoog
authors.forename: Johanna
authors.initials: J
authors.lastname: Smeds
authors.forename: Sara
authors.initials: S
authors.lastname: Wedrén
authors.forename: John
authors.initials: J
authors.lastname: Ohd
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D017931:DNA Primers; D018572:Disease-Free Survival; D015914:Estrogen Replacement Therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017698:Postmenopause; D017697:Premenopause; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D016019:Survival Analysis; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone