title: Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: differences by age, race, and tumor characteristics.
abstract: BACKGROUND
  Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups.
  
  
  METHODS
  We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier.
  
  
  RESULTS
  In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrine-positive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores from PAM50 were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, P Trend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR = 0.5 (95% CI, 0.3-0.9).
  
  
  CONCLUSIONS
  Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes.
  
  
  CONCLUSIONS
  Subtyping in a population-based cohort revealed distinct profiles by age and race.
authors: Authors' Affiliations: Division of Epidemiology, Department of Internal Medicine; Huntsman Cancer Institute, University of Utah; The Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, Utah; and Division of Research, Kaiser Permanente Northern California, Oakland, California.
authors: Carol
authors: C
authors: Sweeney
authors: Philip S
authors: PS
authors: Bernard
authors: Rachel E
authors: RE
authors: Factor
authors: Marilyn L
authors: ML
authors: Kwan
authors: Laurel A
authors: LA
authors: Habel
authors: Charles P
authors: CP
authors: Quesenberry
authors: Kaylynn
authors: K
authors: Shakespear
authors: Erin K
authors: EK
authors: Weltzien
authors: Inge J
authors: IJ
authors: Stijleman
authors: Carole A
authors: CA
authors: Davis
authors: Mark T W
authors: MT
authors: Ebbert
authors: Adrienne
authors: A
authors: Castillo
authors: Lawrence H
authors: LH
authors: Kushi
authors: Bette J
authors: BJ
authors: Caan
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000235:genetics* / 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; 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