Featured Research

from universities, journals, and other organizations

Genetic Variation Of Enzyme Linked With Outcomes For Women Receiving Tamoxifen

Date:
November 2, 2009
Source:
JAMA and Archives Journals
Summary:
Among women with early stage breast cancer, genetic variation of a certain enzyme appears to be associated with clinical outcomes for women treated with tamoxifen, according to a new study.

Among women with early stage breast cancer, genetic variation of a certain enzyme appears to be associated with clinical outcomes for women treated with tamoxifen, according to a study in the October 7 issue of JAMA.

"Tamoxifen has been the gold standard for the last 25 years for endocrine treatment of breast cancer. It is estimated that the lives of half a million women have been saved with adjuvant [supplemental] tamoxifen therapy," according to background information in the article. The growth inhibitory effect of tamoxifen is mediated by its metabolites, 4-hydroxytamoxifen and endoxifen. The formation of active metabolites is brought about by the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme. "Approximately 100 CYP2D6 genetic variants have been identified, which manifest in the population in 4 distinct phenotypes, extensive (normal activity), intermediate (reduced activity), poor (no activity), and ultrarapid (high activity) metabolism, and a gene-dose effect with respect to endoxifen plasma concentrations has been demonstrated. Thus, it can be speculated that genotype-related differences in the formation of active metabolites influence therapeutic response to tamoxifen."

Werner Schroth, D.Phil., of the Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany, and colleagues conducted a study to determine whether CYP2D6 variation is associated with clinical outcomes in women receiving tamoxifen as a supplemental treatment. The study included 1,325 patients who had diagnoses of stage I through III breast cancer between 1986 and 2005 and who were mainly postmenopausal (95.4 percent). Last follow-up was in December 2008, and the median (midpoint) follow-up time was 6.3 years. DNA from tumor tissue or blood was genotyped for CYP2D6 variants associated with reduced or absent enzyme activity. Women were classified as having an extensive (n = 609), heterozygous extensive/intermediate (n = 637), or poor (n = 79) CYP2D6 metabolism.

The researchers found higher breast cancer event rates in patients with reduced or absent CYP2D6 function vs. extensive metabolism patients. "At 9 years of follow-up, the recurrence rates were 14.9 percent for extensive metabolizers, 20.9 percent for heterozygous extensive/intermediate metabolizers, and 29.0 percent for poor metabolizers, and all-cause mortality rates were 16.7 percent, 18.0 percent, and 22.8 percent, respectively," the authors write. Compared with extensive metabolizers, heterozygous extensive/intermediate metabolizers had a 40 percent increased risk of recurrence; poor metabolizers had nearly twice the risk.

"Compared with extensive metabolizers, those with decreased CYP2D6 activity (heterozygous extensive/intermediate and poor metabolism) had worse event-free survival and disease-free survival, but there was no significant difference in overall survival."

"Genotyping has the potential for identification of women who have the CYP2D6 poor metabolism phenotype and for whom the use of tamoxifen is associated with poor outcomes, thus indicating consideration of alternative forms of adjuvant endocrine therapy," the authors conclude.


Story Source:

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


Journal Reference:

  1. Werner Schroth; Matthew P. Goetz; Ute Hamann; Peter A. Fasching; Marcus Schmidt; Stefan Winter; Peter Fritz; Wolfgang Simon; Vera J. Suman; Matthew M. Ames; Stephanie L. Safgren; Mary J. Kuffel; Hans Ulrich Ulmer; Julia Bolander; Reiner Strick; Matthias W. Beckmann; Heinz Koelbl; Richard M. Weinshilboum; James N. Ingle; Michel Eichelbaum; Matthias Schwab; Hiltrud Brauch. Association Between CYP2D6 Polymorphisms and Outcomes Among Women With Early Stage Breast Cancer Treated With Tamoxifen. JAMA, 2009; 302 (13): 1429-1436

Cite This Page:

JAMA and Archives Journals. "Genetic Variation Of Enzyme Linked With Outcomes For Women Receiving Tamoxifen." ScienceDaily. ScienceDaily, 2 November 2009. <www.sciencedaily.com/releases/2009/10/091006161808.htm>.
JAMA and Archives Journals. (2009, November 2). Genetic Variation Of Enzyme Linked With Outcomes For Women Receiving Tamoxifen. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2009/10/091006161808.htm
JAMA and Archives Journals. "Genetic Variation Of Enzyme Linked With Outcomes For Women Receiving Tamoxifen." ScienceDaily. www.sciencedaily.com/releases/2009/10/091006161808.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