Mayo Clinic researchers report that the expression of two novel genes within the tumors of women with early stage breast cancer may allow identification of women who are and are not at risk for early relapse or cancer-related death. Results of the study are published in the April 1 issue of Clinical Cancer Research.

"The HOXB13 and IL17BR gene profile was previously discovered as a potential marker of relapse in hormone-receptor positive breast cancer treated with tamoxifen," says Matthew Goetz, M.D., who co-led the project with James Ingle, M.D. and Fergus Couch, Ph.D. "Our new study shows that the marker is only useful for identifying women with a higher risk in the setting of lymph node-negative breast cancer."

The study, which was conducted by researchers at Mayo Clinic, Harvard Medical School and Arcturus Bioscience, tested whether the expression levels of two genes within women with early stage breast cancer affected the outcomes of women with estrogen receptor-positive breast cancer. The research team examined tissue from 206 postmenopausal women enrolled in a prospective study conducted by the North Central Cancer Treatment Group (NCCTG). They tested the level of gene expression of HOXB13 and IL17BR from paraffin-embedded tumors and found that the 2-gene expression ratio was an independent marker of early breast cancer relapse or death in lymph node-negative breast cancer.

"We believe that these findings are clinically important and corroborate the accumulating laboratory data which suggests that the HOXB13 gene is critically involved in breast cancer metastases," says Dr. Goetz. "Further research is needed to determine whether more aggressive or additional treatments will improve the outcomes of women identified to be at high risk by means of this marker."

Breast cancer is diagnosed in approximately one million women each year, and claims the lives of over 40,000 in the United States. More than two-thirds of all breast cancers are hormone positive, and most of these are early stage (lymph node-negative).

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"Brainy children are not cleverer solely by virtue of having more or less gray matter at any one age," explained Rapoport. "Rather, IQ is related to the dynamics of cortex maturation." The observed differences are consistent with findings from functional magnetic resonance imaging, showing that levels of activation in prefrontal areas correlates with IQ, note the researchers. They suggest that the prolonged thickening of prefrontal cortex in children with superior IQs might reflect an "extended critical period for development of high-level cognitive circuits." Although it's not known for certain what underlies the thinning phase, evidence suggests it likely reflects "use-it-or-lose-it" pruning of brain cells, neurons, and their connections as the brain matures and becomes more efficient during the teen years.

"People with very agile minds tend to have a very agile cortex," said Shaw. The NIMH researchers are following-up with a search for gene variants that might be linked to the newly discovered trajectories. However, Shaw notes mounting evidence suggesting that the effects of genes often depends on interactions with environmental events, so the determinants of intelligence will likely prove to be a very complex mix of nature and nurture.

Also participating in the study were Drs. Dede Greenstein, Liv Clasen, Rhoshel Lenroot, and Nitin Gogtay, Child Psychiatry Branch, NIMH; and Drs. Jason Lerch and Alan Evans, Montreal Neurological Institute, McGill University.

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