Gene expression profile predicts breast cancer metastases

Researchers have identified a gene expression signature that is a powerful predictor of distant metastases in patients with lymph node-negative breast cancer.

“Since only 30% to 40% of untreated lymph node-negative patients develop tumor recurrence, our prognostic signature could provide a powerful tool to identify those patients at low risk, preventing overtreatment in substantial numbers of patients,” senior author Dr. John Foekens, from Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues note. As reported in the February 19th issue of The Lancet, the researchers analyzed 22,000 RNA transcripts from breast cancer samples to identify an expression profile that predicted metastases. The samples came from 286 patients with node-negative disease.Using a training set of 115 tumor specimens, the authors identified a 76-gene signature that predicted distant metastases. Subsequent testing of this signature in a set of 171 lymph node-negative patients yielded a sensitivity and specificity of 93% and 48%, respectively.The profile was found to be useful in predicting metastatic disease even after adjusting for traditional prognostic factors. Moreover, the signature was particularly good at predicting metastases within 5 years; patients with the signature were nearly six times more likely to develop metastases than patients lacking this profile.The investigators found that the signature was a strong predictor of metastases regardless of menopausal status and also performed well in patients with tumors between 10 to 20 mm, a group that has traditionally proved to be a prognostic challenge.In a related editorial, Dr. Tor-Kristian Jenssen, from PubGene AS in Vinderen, Norway, and Dr. Eivind Hovig, from the Norwegian Radium Hospital in Montebello, note that although the current study represents the largest of its kind to date, “it may still be too small to provide a final selection of genes for signature inclusion. Thus, the signature is there, but it is still necessary to read the fine print.”(Source: Lancet 2005;365:634-635,671-679: Reuters Health: Oncolink: February 2005.)