PT  - JOURNAL ARTICLE
AU  - Caan, Bette J.
AU  - Sweeney, Carol
AU  - Habel, Laurel A.
AU  - Kwan, Marilyn L.
AU  - Kroenke, Candyce H.
AU  - Weltzien, Erin K.
AU  - Quesenberry, Charles P.
AU  - Castillo, Adrienne
AU  - Factor, Rachel E.
AU  - Kushi, Lawrence H.
AU  - Bernard, Philip S.
TI  - Intrinsic Subtypes from the PAM50 Gene Expression Assay in a Population-Based Breast Cancer Survivor Cohort: Prognostication of Short- and Long-term Outcomes
AID  - 10.1158/1055-9965.EPI-13-1017
DP  - 2014 May 01
TA  - Cancer Epidemiology Biomarkers & Prevention
PG  - 725--734
VI  - 23
IP  - 5
4099  - http://cebp.aacrjournals.org/content/23/5/725.short
4100  - http://cebp.aacrjournals.org/content/23/5/725.full
SO  - Cancer Epidemiol Biomarkers Prev2014 May 01; 23
AB  - 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. Cancer Epidemiol Biomarkers Prev; 23(5); 725–34. ©2014 AACR.See related article by Sweeney et al., p. 714This article is featured in Highlights of This Issue, p. 685