title: Intrinsic subtypes from the PAM50 gene expression assay in a population-based breast cancer survivor cohort: prognostication of short- and long-term outcomes.
abstract: BACKGROUND
  The PAM50, a gene expression assay to categorize breast tumors into intrinsic subtypes, has not been previously used to examine short- and long-term prognostication in a population-based cohort where treatment patterns and time of initial follow-up vary.
  
  
  METHODS
  In a stratified case-cohort design of 1,691 women from the LACE and Pathways breast cancer survivor cohorts, we used PAM50 to categorize tumors into Luminal A (LumA), Luminal B (LumB), HER2-enriched (HER2-E), Basal-like and Normal-like, and to examine risk of early and late recurrence and mortality by Cox proportional hazards regression.
  
  
  RESULTS
  Compared with LumA, cumulative risk of recurrence and breast cancer death was higher for LumB, HER2-E, and Basal-like tumors at 2, 5, and 10 years. However, HR of breast cancer death varied over time [<5 years (early) vs. > 5 years (late)] for both Basal-like (HR, 6.23 early vs. HR, 0.63 late) and HER2-E tumors (HR, 2.97 early vs. HR, 0.73 late) but not for LumB tumors where risk was elevated consistently (HR, 2.67 early vs. HR, 1.47 late). The contrast between LumB, HER2-E, and Basal-like compared with LumA on early recurrence was stronger when subtype was defined by PAM50 than by immunohistochemistry (IHC) markers.
  
  
  CONCLUSIONS
  The PAM50 categorized intrinsic subtypes in a manner that more accurately predicts recurrence and survival, especially for luminal tumors, compared with commonly used methods that rely on traditional IHC clinical markers.
  
  
  CONCLUSIONS
  The PAM50 is robust for use in epidemiologic studies and should be considered when archived tumor tissues are available.
authors: Authors' Affiliations: Division of Research, Kaiser Permanente Northern California, Oakland, California; Department of Internal Medicine, Division of Epidemiology; Huntsman Cancer Institute, University of Utah; and The Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, Utah.
authors: Bette J
authors: BJ
authors: Caan
authors: Carol
authors: C
authors: Sweeney
authors: Laurel A
authors: LA
authors: Habel
authors: Marilyn L
authors: ML
authors: Kwan
authors: Candyce H
authors: CH
authors: Kroenke
authors: Erin K
authors: EK
authors: Weltzien
authors: Charles P
authors: CP
authors: Quesenberry
authors: Adrienne
authors: A
authors: Castillo
authors: Rachel E
authors: RE
authors: Factor
authors: Lawrence H
authors: LH
authors: Kushi
authors: Philip S
authors: PS
authors: Bernard
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D044469:Racial Groups; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C506487:ESR1 protein, human; C508053:ERBB2 protein, human