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Capacity to Metabolize Hormone Therapy Influences Breast Cancer Recurrence

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Genetic changes influence cancer recurrence and death

When determining how well tamoxifen works, new study results provide evidence that genetic differences in the enzyme CYP2D6 play a key role.

Mayo Clinic oncologist Matthew Goetz, MD, lead author of the study published in the journal Clinical Cancer Research, says, “Our findings confirm that, in early breast cancer treated with tamoxifen, genetic alterations in CYP2D6 lead to a higher likelihood of recurrence and death.”

For the trial, Goetz and colleagues from the Mayo Clinic Cancer Center and the Austrian Breast and Colorectal Cancer Study Group studied cancer recurrence and death rates in 2 groups. One set of patients included postmenopausal women with primary estrogen receptor–positive breast cancer who received tamoxifen for 5 years, while the other group received tamoxifen for 2 years followed by the aromatase inhibitor anastrozole for 3 years.

Compared with women with normal CYP2D6 enzyme activity, study results showed that women born with genetic alterations in CYP2D6 that abolish the enzyme’s critical metabolizing activity and who took tamoxifen for 5 years had recurrence of breast cancer or died at a rate 2.5 times higher. Rates of recurrence or death were 1.7 times higher in women with intermediate levels of the CYP2D6 enzyme.

However, genetic alterations in CYP2D6 did not affect the chance of recurrence or death in women who switched to anastrozole after 2 years of tamoxifen, Goetz notes.

Senior author James Ingle, MD, of Mayo Clinic, an expert on hormone therapies for breast cancer says, “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.”

For women with decreased CYP2D6 metabolism, Goetz believes that the current recommendation of switching from tamoxifen to an aromatase inhibitor is likely to result in the greatest benefit. The best approach for women with poor CYP2D6 metabolism may be to avoid tamoxifen altogether and begin with an aromatase inhibitor, he says.

Source: Mayo Clinic.