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

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

Author information

1
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.

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.

PMID:
24521998
PMCID:
PMC4105204
DOI:
10.1158/1055-9965.EPI-13-1017
[Indexed for MEDLINE]
Free PMC Article

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