Gene Signature Correlates With Survival in Breast Cancer Patients

The gene signature, which is associated with the transforming growth factor-beta (TGF-ß) signaling pathway, correlates with reduced relapse-free survival in patients with breast cancer, especially in those with estrogen receptor (ER) positive tumors.

TGF-ß is a regulator of tumor growth and metastasis. In the early stages of cancer, TGF-ß signaling inhibits tumor growth. Most tumors eventually lose their sensitivity to TGF-ß, and the initially beneficial protein begins promoting tumor growth and metastasis during later cancer stages. Loss of TGF-ß signaling has been linked to tumor progression in human breast cancer.

Prof. Harold Moses, M.D. at the Vanderbilt-Ingram Cancer Center (Nashville, TN, USA) and colleagues probed human breast cancer gene expression profiles available in public databases. They found that the gene signature representing a complete elimination of TGF-ß signaling correlated with significantly reduced relapse-free survival in all patients. The association was even stronger in patients with estrogen receptor (ER) positive tumors, a subtype of breast cancer that responds well to antiestrogen therapies like tamoxifen.

The signature also indicated that chemokines are important mediators of TGF-ß's effects on tumor growth. "I think one of the most significant aspects of this is that it is the first real demonstration that a major function of TGF-ß signaling is to suppress chemokine expression," said Prof. Moses.

The study was published in the May 18, 2009 issue of the Journal of Clinical Investigation

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Vanderbilt-Ingram Cancer Center