Intrinsic subtypes from the PAM50 gene expression assay in a population-based breast cancer survivor cohort: prognostication of short- and long-term outcomes

Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):725-34. doi: 10.1158/1055-9965.EPI-13-1017. Epub 2014 Feb 12.

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.

Impact: The PAM50 is robust for use in epidemiologic studies and should be considered when archived tumor tissues are available.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / classification*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cohort Studies
  • Continental Population Groups
  • Estrogen Receptor alpha / metabolism
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Progesterone / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Estrogen Receptor alpha
  • RNA, Messenger
  • Receptors, Progesterone
  • estrogen receptor alpha, human
  • ERBB2 protein, human
  • Receptor, ErbB-2