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:2/13/2016)... ... ... DDi , a Makro company, makes it to ... in eClinical Solutions. DDi has built its solution competency with a unique blend ... DDi provides smarter technology for Clinical Development, Regulatory and Enterprise domains by providing ...
(Date:2/12/2016)... , ... February 12, 2016 , ... ... devoted exclusively to funding innovative lymphoma research and serving the lymphoma community through ... over 250 members of South Florida’s philanthropic community at its 10th anniversary Fashion ...
(Date:2/12/2016)... ... 2016 , ... Coco Libre, the maker of coconut water beverages with a ... Lounge Event. Coco Libre will offer musicians and celebrities the company’s signature Organic Coconut ... invitation-only gifting suite, held this year at the W Hollywood Hotel, has become a ...
(Date:2/12/2016)... ... February 12, 2016 , ... Fisher House Foundation Chairman ... John J. Lee, Nevada Military Support Alliance president Scott Bensing, and Peggy Kearns Director, ... VA Southern Nevada Healthcare System. This will be the first Fisher House in ...
(Date:2/12/2016)... ... February 12, 2016 , ... Young ... area, celebrates the beginning of the latest charity campaign in their community enrichment ... art. Donations to this worthy cause are currently being accepted at: http://artexpressioninc.org/ ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... , Kalifornien, 12. Februar 2016  Sequent ... der Aufnahme von Patienten für eine Studie zur ... Aneurysmen („WEB") speziell für die Behandlung von rupturierten ... , MD, Leiter der Neuroradiologie an der Universitätsklinik ... und Hauptprüfarzt der CLARYS-Studie hat den ersten Patienten ...
(Date:2/12/2016)... , Feb. 12, 2016  Eli Lilly and Company ... Court decided the Alimta® (pemetrexed disodium) vitamin regimen patent would ... the UK, France , Italy ... to dilute the product only with dextrose solution.  ... 2015, the UK Court of Appeal held that Lilly,s patent ...
(Date:2/12/2016)... BUDAPEST , Ungarn, February 12, 2016 ... ein Medizintechnikunternehmen, das sich auf den ungedeckten ... gab heute positive Ergebnisse seines klinischen Forschungsprogramms ... und Asthma-Patienten beschäftigt, ergab Verbesserungen ihrer respiratorischen ... Indiso ltd , ein Medizintechnikunternehmen, das ...
Breaking Medicine Technology: