Can a Single Gene Defeat Tamoxifen Treatment?

Breast cancer patients with defective CYP2D6 respond better to aromatase inhibitors

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) Not all women respond to a common breast cancer drug called tamoxifen. Not to worry–these women can now be identified and switched to another medication before the disease turns deadly.

Tamoxifen blocks estrogen. It’s commonly used to treat women with the type of breast cancer that feeds on estrogen. A recent study shows that a defect in the enzyme CYP2D6 indicates tamoxifen may not work. That’s because the body doesn’t metabolize the drug well.

A blood test can easily detect this genetic difference. Researchers suggest these patients can be switched to another type of estrogen blocker called an aromatase inhibitor (AI) to continue effective treatment.

"If you’re on tamoxifen, talk to your doctor about genetic testing."

This is the work of researchers at the Mayo Clinic Cancer Center and the Austrian Breast and Colorectal Cancer Study Group.

Lead author, Mayo Clinic oncologist Matthew Goetz, MD, said in a statement, "Our findings confirm that, in early breast cancer treated with tamoxifen, genetic alterations in CYP2D6 lead to a higher likelihood of recurrence and death."

Adam Brufsky, MD, PhD, professor of medicine at the University of Pittsburgh, has some reservations about the results. “This is an interesting study that conflicts with other large studies which state the opposite - that genetic influences on tamoxifen metabolism do not influence survival in hormone receptor positive breast cancer. We will need to reconcile the results of all of these studies to develop firm recommendations,” Dr. Brufsky told dailyRx News.

For this study, the researchers looked at two groups of women who were being treated for estrogen receptor positive (ER+) breast cancer. A total of 3,714 women participated in this phase III clinical trial known as the Austrian Breast and Colorectal Cancer Study Group.

One group included postmenopausal women who took tamoxifen for five years. The other women took tamoxifen for two years and were then switched to the aromatase inhibitor – anastrozole (Arimidex) – for three years.

Aromatase inhibitors (AI) are a different class of drugs that blocks estrogen. Anastrozole doesn’t depend on the CYP2D6 enzyme to work.

Women in the study with the faulty CYP2D6 enzyme who took tamoxifen for five years were 2.5 times more likely to have a recurrence of and die from breast cancer than women with normally functioning CYP2D6. If the enzyme had moderate activity, the women in this group were 1.7 times more likely to have a poor outcome than women with normal CYP2D6 activity.

The women who switched to anastrozole saw no increase in the likelihood of the cancer returning and being fatal.

The researchers say between 5 and 7 percent of breast cancer patients from European and American populations don’t metabolize CYP2D6 well. A blood test that costs about $300 can measure the activity of this enzyme.

Along with anastrozole, two other AIs are available – Femara (letrozole) and Aromasin (exemestane).

This study, which was partially funded by the National Institutes of Health, was published in the December issue of the journal Clinical Cancer Research.

Reviewed by: 
Review Date: 
December 28, 2012
Last Updated:
January 2, 2013