• Bette J Caan, Carol Sweeney, Laurel A Habel, Marilyn L Kwan, Candyce H Kroenke, Erin K Weltzien, Charles P Quesenberry, Adrienne Castillo, Rachel E Factor, Lawrence H Kushi, and Philip S Bernard.
• 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.
• Cancer Epidemiol. Biomarkers Prev. 2014 May 1; 23 (5): 725-34.

BackgroundThe 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.MethodsIn 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.ResultsCompared 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.ConclusionsThe 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.ImpactThe PAM50 is robust for use in epidemiologic studies and should be considered when archived tumor tissues are available.©2014 AACR.

41 keywords...

hide…