Identifying Recurrence Risk in Women Taking Tamoxifen

The findings were reported in the June 2004 issue of Cancer Cell.

Determining those women for whom tamoxifen is likely to fail would allow earlier use of other therapies that might be more effective for them. Tamoxifen blocks the interaction between the hormone estrogen and its receptor protein and is used to treat breast cancers that express the estrogen receptor. Only two thirds of these patients have a prolonged response to the drug.

"Until now, there has been no way to predict which estrogen-receptor-positive patients will not respond to tamoxifen treatment,” said Dennis Sgroi, M.D., director of breast pathology at Massachusetts General Hospital (MGH, Boston, MA, USA; www.massgeneral.org), who led the hospital's research team. "Identifying those for whom tamoxifen is likely to fail could allow physicians to choose other drugs, for instance the aromatase inhibitors that more completely block estrogen's action.”

The researchers gathered tumor samples from patients who had received tamoxifen treatment for early-stage, estrogen-receptor-positive breast cancer. They identified 50 frozen samples suitable for gene expression analysis, for which clinical follow-up information was available. Of those 60 patients, 32 had remained disease-free for an average of eight years, while 28 had recurrence of their tumor or metastasis.

Expression profile analysis demonstrated that the ratio between the expression levels of two genes, HOXB13 and IL17BR, was the strongest predictor of whether a tumor would recur. The higher the expression level of HOXB3 and the lower the expression of IL17BR, the greater the chance of tumor recurrence. Data from an additional 20 samples of tamoxifen-treated tumors supported the predictive power of the two-gene expression ratio. The study was conducted by researchers at Massachusetts General Hospital Cancer Center and Arcturus Bioscience, Inc. (Mountain View, CA, USA).

Because HOXB13 is known to be overexpressed in some breast tumors, the researchers investigated whether the gene might also play a role in tumor development. Using cells from normal breast tissues, they induced the expression of the HOXB13 gene. Cells in which the gene was activated showed obvious structural changes and appeared to have an increased ability to move and invade other tissues, characteristic of tumor cells. While that result must be confirmed by future studies, it suggests that the pathway controlled by HOXB13 could be a new therapeutic target.

"Many clinical laboratories currently have the capacity to utilize the Arcturus technology to measure the relative expression of these two genes,” noted Mark Erlander, Ph.D., chief scientific officer of Arcturus, "Several centralized laboratories are developing a test that will be available this summer.”

Arcturus is a leading company in laser microdissection instruments and reagents for the analysis of microscopic tissue samples. These tools enable researchers to perform rapid cell-based analysis of disease progression utilizing the smallest and purest samples possible to date.




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