Gene Testing may be Key for Treating Some Women with Breast Cancer

Findings from a new study prompt Mayo Clinic researchers to recommend CYP2D6 gene testing for postmenopausal women about to begin tamoxifen therapy. New data confirms that women with an inherited deficiency in the CYP2D6 gene important for the metabolism of tamoxifen have a nearly 4-fold higher risk of early breast cancer recurrence compared to women who have not inherited the deficiency.

The findings will be presented today at the CTRC-AACR San Antonio Breast Cancer Symposium

Tamoxifen, FDA approved for the prevention and recurrence of estrogen-receptor-positive (ER+) breast cancer, is a “pro-drug,” which means that it must be metabolized in the liver to become active. Mayo researchers had earlier discovered that the drug is less effective in postmenopausal breast cancer patients who had a deficiency in the CYP2D6 gene, which is key for activating tamoxifen as well as many other drugs. However, up until now, testing has not been done routinely at most centers.

“These new results validate our earlier findings,” says the study’s lead investigator, Matthew Goetz, M.D., an assistant professor of oncology and of 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 3900 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% reduced risk of developing breast cancer recurrence compared to staying on tamoxifen.

The findings reported by Mayo and ABCSG highlight an emerging science termed pharmacogenomics, in which researchers are studying whether genetic differences in how patients metabolize or process drugs can be used to individualize therapy.

This research was funded by R01 CA133049-01 (Goetz) Austrian Breast and Colorectal Study Group, bioTheranostics, Mayo Clinic Cancer Center, Mayo Clinic Breast Cancer SPORE (CA116201), and the Commonwealth Cancer Research Foundation.

Mayo Clinic has a potential financial interest in technology related to this research. Dr. Matthew Goetz, Dr. James Ingle, Dr. Matthew Ames and Mayo Clinic have a potential financial interest in two technologies, CYP2D6 and the combined HOXB13/IL17BR and CYP2D6, studied in this research and may stand to gain financially from the successful outcome of this research.