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Confounding Effects in "A Six-Gene Signature Predicting Breast Cancer Lung Metastasis"

Departments of ¹ Biostatistics and Computational Biology and ² Cancer Biology, Dana-Farber Cancer Institute and ³ Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts

Requests for reprints: John Quackenbush, Dana-Farber Cancer Institute, 44 Binney Street, Sm822, Boston, MA 02115. Phone: 617-582-8163; Fax: 617-582-7760; E-mail: johnq{at}jimmy.harvard.edu.

Key Words: Breast Cancer • Confounding Effects • Predictive Expression Signatures

Abstract

The majority of breast cancer deaths result from metastases rather than from direct effects of the primary tumor itself. Recently, Landemaine and colleagues described a six-gene signature purported to predict lung metastasis risk. They analyzed gene expression in 23 metastases from breast cancer patients (5 lung, 18 non-lung) identifying a 21-gene signature. Expression of 16 of these was analyzed in primary breast tumors from 72 patients with known outcome, and six were selected that were predictive of lung metastases: DSC2, TFCP2L1, UGT8, ITGB8, ANP32E, and FERMT1. Despite the value of such a signature, our analysis indicates that this analysis ignored potentially important confounding factors and that their signature is instead a surrogate for molecular subtype. [Cancer Res 2009;69(18):7480–5]