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Mayo Clinic research on tamoxifen leads to recommendation for CYP2D6 gene test
Date:12/13/2008

etz, M.D., an assistant professor of oncology and pharmacology at Mayo Clinic, "and strongly suggest that going forward, postmenopausal patients being considered for tamoxifen therapy should be tested for CYP2D6 before beginning therapy."

The research teams examined DNA from a subset of postmenopausal women treated in the ABCSG-8 study, which previously randomized nearly 3,900 women whose ER+ breast cancer had been surgically treated. One group was randomized to five years of tamoxifen therapy, and the other randomized to tamoxifen for two years followed by three years of anastrozole, an aromatase inhibitor. The initial results of ABCSG-8, reported in 2005, concluded that women who switched to anastrozole had a 40 percent reduced risk of breast cancer recurrence compared to staying on tamoxifen.

The aim of the new study was to determine whether CYP2D6 genetic variation would identify a subgroup of patients at higher risk of recurrence within the context of the ABCSG-8 trial. "Among the patients randomized to tamoxifen, poor metabolizers had a 3.8-fold increase in risk of developing breast cancer recurrence than extensive metabolizers across the five-year span," said Michael Gnant, M.D., professor of Surgery at the Medical University of Vienna, Austria, and president of ABCSG. "That is the key message coming out of this great collaboration between the Mayo Clinic team and the Austrian Breast and Colorectal Cancer Study Group."

However, the researchers also demonstrated that among patients who switched to anastrozole, there was no increased risk of breast cancer recurrence for CYP2D6 poor metabolizers in years three to five. The benefit of switching to anastrozole, says Dr. Goetz, may be most pronounced in the group of patients with deficient CYP2D6 metabolism. "Poor metabolizers who were fortunate to not develop breast cancer recurrence in the first two years of tamoxifen appear to be rescued by anastrozole," he says.

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Contact: Karl Oestreich
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
Source:Eurekalert

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