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Concordance among Gene-Expression–Based Predictors for Breast Cancer

Cheng Fan, M.S., Daniel S. Oh, Ph.D., Lodewyk Wessels, Ph.D., Britta Weigelt, Ph.D., Dimitry S.A. Nuyten, M.D., Andrew B. Nobel, Ph.D., Laura J. van't Veer, Ph.D., and Charles M. Perou, Ph.D. acer.gif ABSTRACT

Background Gene-expression–profiling studies of primary breast tumors performed by different laboratories have resulted in the identification of a number of distinct prognostic profiles, or gene sets, with little overlap in terms of gene identity.

Methods To compare the predictions derived from these gene sets for individual samples, we obtained a single data set of 295 samples and applied five gene-expression–based models: intrinsic subtypes, 70-gene profile, wound response, recurrence score, and the two-gene ratio (for patients who had been treated with tamoxifen).

Results We found that most models had high rates of concordance in their outcome predictions for the individual samples. In particular, almost all tumors identified as having an intrinsic subtype of basal-like, HER2-positive and estrogen-receptor–negative, or luminal B (associated with a poor prognosis) were also classified as having a poor 70-gene profile, activated wound response, and high recurrence score. The 70-gene and recurrence-score models, which are beginning to be used in the clinical setting, showed 77 to 81 percent agreement in outcome classification.

Conclusions Even though different gene sets were used for prognostication in patients with breast cancer, four of the five tested showed significant agreement in the outcome predictions for individual patients and are probably tracking a common set of biologic phenotypes.




Source Information

From the Departments of Genetics (C.F., D.S.O., C.M.P.), Statistics and Operations Research (A.B.N.), and Pathology and Laboratory Medicine (C.M.P.), University of North Carolina at Chapel Hill and Lineberger Comprehensive Cancer Center, Chapel Hill; and the Divisions of Diagnostic Oncology (L.W., B.W., L.J.V.) and Radiotherapy (D.S.A.N.), the Netherlands Cancer Institute, Amsterdam.

Drs. Fan and Oh contributed equally to this article.