Genetic differences in enzyme CYP2D6 play a key role in effectiveness of tamoxifen for breast cancer

Published on December 27, 2012 at 5:57 AM · No Comments

For nearly a decade, breast cancer researchers studying the hormone therapy tamoxifen have been divided as to whether genetic differences in a liver enzyme affect the drug's effectiveness and the likelihood breast cancer will recur. A new study by researchers from the Mayo Clinic Cancer Center (http://mayoresearch.mayo.edu/mayo/research/cancer-research/contact.cfm) and the Austrian Breast and Colorectal Cancer Study Group (http://www.breastinternationalgroup.org/Membership/BIGMembers/ABCSG.aspx) provides evidence that genetic differences in the enzyme CYP2D6 play a key role in how well tamoxifen works.

"Our findings confirm that, in early breast cancer treated with tamoxifen, genetic alterations in CYP2D6 lead to a higher likelihood of recurrence and death," says Mayo Clinic (http://www.mayoclinic.org/) oncologist Matthew Goetz, M.D.,(http://mayoresearch.mayo.edu/mayo/research/staff/goetz_mp.cfm) lead author of the study in the journal Clinical Cancer Research.

In the clinical trial, Dr. Goetz and his colleagues studied the rates of cancer recurrence and death in two groups: postmenopausal women with primary estrogen receptor-positive breast cancer who received tamoxifen for five years and those who received tamoxifen for two years followed by the aromatase inhibitor anastrozole for three years. Anastrozole is a breast cancer drug whose metabolism does not require the CYP2D6 enzyme.

The study showed that women who were born with genetic alterations of CYP2D6 that abolish the enzyme's critical metabolizing activity and who took tamoxifen for five years had recurrence of breast cancer, or died at a rate 2.5 times higher than women with normal CYP2D6 enzyme activity. Women with intermediate levels of the CYP2D6 enzyme had rates of recurrence or death 1.7 times higher than women with normal CYP2D6 activity. Importantly, Dr. Goetz notes, that genetic alterations in CYP2D6 did not affect the likelihood of recurrence or death in women who switched to anastrozole after two years of tamoxifen.

"Switching from tamoxifen to an aromatase inhibitor may be one reason for the discrepant studies surrounding CYP2D6 and tamoxifen -- as information about whether a patient took an aromatase inhibitor after tamoxifen was not available in most of the prior studies," says senior author James Ingle, M.D., of Mayo Clinic, an expert on hormone therapies for breast cancer.

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