Featured Research

from universities, journals, and other organizations

Ability to metabolize tamoxifen affects breast cancer outcomes

Date:
December 26, 2012
Source:
Mayo Clinic
Summary:
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 provides evidence that genetic differences in the enzyme CYP2D6 play a key role in how well tamoxifen works.

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 and the Austrian Breast and Colorectal Cancer Study Group 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 oncologist Matthew Goetz, M.D., 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.

A blood test can determine whether a woman has alterations in CYP2D6 and predict how efficiently her body will convert tamoxifen to endoxifen. Approximately 5 to 7 percent of European and North American populations are considered poor metabolizers of tamoxifen.

"The results of this successful high-level international research collaboration are an important step forward in our quest to individualize breast cancer treatment and provide tailored care to women with breast cancer," says Michael Gnant, M.D., professor of surgery at the Medical University of Vienna and president of the Austrian study group.

So what should a woman do if she is unable to effectively metabolize tamoxifen into its most active form? Dr. Goetz believes that the current recommendation of switching from tamoxifen to an aromatase inhibitor is likely to result in the greatest benefit in women with decreased CYP2D6 metabolism. For CYP2D6 poor metabolizers, avoiding tamoxifen altogether and starting out with an aromatase inhibitor may be the best approach, he says.

Dr. Goetz's group is working with the National Cancer Institute to develop endoxifen as an alternative to tamoxifen. If women can be given endoxifen, the active part of tamoxifen, it won't matter how tamoxifen gets metabolized, he says.

The study is partially funded by the National Institutes of Health, co-authors include Vera Suman, Ph.D.; Tanya Hoskin; Mary Kuffel; Stephanie Safgren; Carol Reynolds, M.D.; Matthew Ames, Ph.D.; and Richard Weinshilboum, M.D., all of Mayo Clinic; Martin Filipits, Ph.D.; Raimund Jakesz and Margaretha Rudas of the Medical University of Vienna; Richard Greil and Otto Dietze of Paracelsus Medical University, Salzburg, Austria; and Alois Lange and Felix Offner of Medical Hospital Feldkirch, Austria.


Story Source:

The above story is based on materials provided by Mayo Clinic. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. P. Goetz, V. Suman, T. L. Hoskin, M. Gnant, M. Filipits, S. Safgren, M. J. Kuffel, R. Jakesz, M. Rudas, R. Greil, O. Dietze, A. Lang, F. Offner, C. A. Reynolds, R. M. Weinshilboum, M. Ames, J. N. Ingle. CYP2D6 Metabolism and Patient Outcome in the Austrian Breast and Colorectal Cancer Study Group Trial (ABCSG) 8. Clinical Cancer Research, 2012; DOI: 10.1158/1078-0432.CCR-12-2153

Cite This Page:

Mayo Clinic. "Ability to metabolize tamoxifen affects breast cancer outcomes." ScienceDaily. ScienceDaily, 26 December 2012. <www.sciencedaily.com/releases/2012/12/121226153030.htm>.
Mayo Clinic. (2012, December 26). Ability to metabolize tamoxifen affects breast cancer outcomes. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2012/12/121226153030.htm
Mayo Clinic. "Ability to metabolize tamoxifen affects breast cancer outcomes." ScienceDaily. www.sciencedaily.com/releases/2012/12/121226153030.htm (accessed April 16, 2014).

Share This



More Health & Medicine News

Wednesday, April 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com
Cognitive Function: Is It All Downhill From Age 24?

Cognitive Function: Is It All Downhill From Age 24?

Newsy (Apr. 15, 2014) A new study out of Canada says cognitive motor performance begins deteriorating around age 24. Video provided by Newsy
Powered by NewsLook.com
How Mt. Everest Helped Scientists Research Diabetes

How Mt. Everest Helped Scientists Research Diabetes

Newsy (Apr. 15, 2014) British researchers were able to use Mount Everest's low altitudes to study insulin resistance. They hope to find ways to treat diabetes. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins