Navigation Links
Genetic variation of enzyme linked with outcomes for women receiving tamoxifen
Date:10/6/2009

This release is available in Chinese.

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.


'/>"/>

Contact: Hiltrud Brauch, D.Phil.
hiltrud.brauch@ikp-stuttgart.de
JAMA and Archives Journals
Source:Eurekalert

Related medicine news :

1. IBM Research Aims to Build Nanoscale DNA Sequencer to Help Drive Down Cost of Personalized Genetic Analysis
2. New type of genetic change identified in inherited cancer
3. UCLA study identifies 2 chemicals that could lead to new drugs for genetic disorders
4. Johns Hopkins epigenetic center receives $16.8 million NIH grant
5. Cancer predisposition from genetic variation shows strong gender bias
6. Genetics Linked to Early Sexual Activity in Kids
7. Finding of genetic region controlling cardiovascular sensitivity to anesthetic propofol
8. VitaPath Genetics Raises $6M in Series A Round
9. Scientists from University of Hawaii at Manoa find genetic marker
10. NIH study reveals new genetic culprit in deadly skin cancer
11. Genetic Clues May Lead to New Skin Cancer Therapies
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... Experts from the American Institutes ... Research Meeting June 26-28, 2016, at the Hynes Convention Center in Boston. , ... advance care planning, healthcare costs and patient and family engagement. , AIR researchers ...
(Date:6/25/2016)... ... 2016 , ... "With 30 hand-drawn hand gesture animations, FCPX users can easily ... of Pixel Film Studios. , ProHand Cartoon’s package transforms over 1,300 hand-drawn pictures ... . Simply select a ProHand generator and drag it above media or text in ...
(Date:6/25/2016)... ... June 25, 2016 , ... ... non-athletes recover from injury. Recently, he has implemented orthobiologic procedures as a method ... —Johnson is one of the first doctors to perform the treatment. Orthobiologics are ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article published June 14 ... The article goes on to state that individuals are now more comfortable seeking to ... operations such as calf and cheek reduction. The Los Angeles area medical group, Beverly ...
(Date:6/24/2016)... ... 2016 , ... Marcy was in a crisis. Her son James, eight, was out of control. ... and physically. , “When something upset him, he couldn’t control his emotions,” remembers Marcy. ... rocks at my other children and say he was going to kill them. If ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... ANGELES , June 23, 2016 ... CAPR ), a biotechnology company focused ... therapeutics, today announced that patient enrollment in its ... in Duchenne) has exceeded 50% of its 24-patient ... enrollment in the third quarter of 2016, and ...
(Date:6/23/2016)... PARK RIDGE, Ill. and INDIANAPOLIS ... caliber of students receiving a Lilly Diabetes Tomorrow,s Leaders ... hands. The 2016 scholarship winners, announced today online at ... refused to let type 1 diabetes stand in the ... Lilly Diabetes has supported the Foundation,s scholarship program since ...
(Date:6/23/2016)... Pa. , June 23, 2016 The ... in an outpatient dialysis facility.  Treatments are usually 3 ... 6 hours per visit, including travel time, equipment preparation ... a patient, but especially grueling for patients who are ... of a skilled nursing and rehabilitation centers for some ...
Breaking Medicine Technology: