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. 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

Bette J Caan  1 , Carol Sweeney, Laurel A Habel, Marilyn L Kwan, Candyce H Kroenke, Erin K Weltzien, Charles P Quesenberry Jr, Adrienne Castillo, Rachel E Factor, Lawrence H Kushi, Philip S Bernard
Affiliations

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

Bette J Caan et al. Cancer Epidemiol Biomarkers Prev. 2014 May.

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.

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Conflict of interest statement

Potential conflict of interest: PSB has an interest in Bioclassifier LLC. The other authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Kaplan-Meier Estimates for Breast Cancer Survival and Recurrence, by PAM50 Subtype
Figure 2
Figure 2
Kaplan-Meier Estimates for Breast Cancer Survival and Recurrence, by Early Entry (Pathways Study) vs. Late Entry (LACE Study) for Basal-like and Luminal B Tumors compared with Luminal A Tumors
See this image and copyright information in PMC

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