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A Six-Gene Signature Predicting Breast Cancer Lung Metastasis

¹ Centre René Huguenin, Fédération Nationale des Centres de Lutte Contre le Cancer and ² Institut National de la Sante et de la Recherche Medicale, U735, Saint-Cloud, France; ³ Proskelia, Romainville, France; ⁴ Metastasis Research Laboratory, Center of Experimental Cancer Research, University of Liège, Liège, Belgium; ⁵ Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy; and ⁶ Center of Molecular Oncology, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain

Requests for reprints: Keltouma Driouch, Institut National de la Sante et de la Recherche Medicale U735/Oncogénétique, Centre René Huguenin, 35 rue Dailly, 92210 Saint-Cloud, France. Phone: 331-47-11-15-66; Fax: 331-47-11-16-96; E-mail: k.driouch{at}stcloud-huguenin.org.

Key Words: gene • expression • signature • lung • metastasis

The lungs are a frequent target of metastatic breast cancer cells, but the underlying molecular mechanisms are unclear. All existing data were obtained either using statistical association between gene expression measurements found in primary tumors and clinical outcome, or using experimentally derived signatures from mouse tumor models. Here, we describe a distinct approach that consists of using tissue surgically resected from lung metastatic lesions and comparing their gene expression profiles with those from nonpulmonary sites, all coming from breast cancer patients. We show that the gene expression profiles of organ-specific metastatic lesions can be used to predict lung metastasis in breast cancer. We identified a set of 21 lung metastasis–associated genes. Using a cohort of 72 lymph node–negative breast cancer patients, we developed a 6-gene prognostic classifier that discriminated breast primary cancers with a significantly higher risk of lung metastasis. We then validated the predictive ability of the 6-gene signature in 3 independent cohorts of breast cancers consisting of a total of 721 patients. Finally, we show that the signature improves risk stratification independently of known standard clinical variables and a previously established lung metastasis signature based on an experimental breast cancer metastasis model. [Cancer Res 2008;68(15):6092–9]

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				K. Driouch, F. Bonin, S. Sin, G. Clairac, and R. Lidereau Confounding Effects in "A Six-Gene Signature Predicting Breast Cancer Lung Metastasis": Reply Cancer Res., December 15, 2009; 69(24): 9507 - 9511. [Abstract] [Full Text] [PDF]

				A. C. Culhane and J. Quackenbush Confounding Effects in "A Six-Gene Signature Predicting Breast Cancer Lung Metastasis" Cancer Res., September 15, 2009; 69(18): 7480 - 7485. [Abstract] [Full Text] [PDF]