Culhane, AedinQuackenbush, John2016-10-132009Culhane, A. C., and J. Quackenbush. 2009. “Confounding Effects in ‘A Six-Gene Signature Predicting Breast Cancer Lung Metastasis.’” Cancer Research 69 (18) (September 1): 7480–7485. doi:10.1158/0008-5472.can-08-3350.0008-5472http://nrs.harvard.edu/urn-3:HUL.InstRepos:29004171The 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.en-USJournal Article2016-10-1310.1158/0008-5472.CAN-08-3350