Navigation Links
Mayo Clinic research on tamoxifen leads to recommendation for CYP2D6 gene test
Date:12/13/2008

SAN ANTONIO - Findings from a new study have prompted Mayo Clinic researchers to recommend CYP2D6 gene testing for postmenopausal women about to begin tamoxifen therapy. This data confirms that women with an inherited deficiency in the CYP2D6 gene, which is important for the metabolism of tamoxifen, have a nearly fourfold higher risk of early breast cancer recurrence compared to women who have not inherited the deficiency. The research findings, announced jointly by investigators from Mayo Clinic and the Austrian Breast and Colorectal Cancer Study Group (ABCSG) confirmed results from a previous study conducted by Mayo Clinic.

VIDEO ALERT: Additional audio and video resources, including excerpts from an interview with Dr. Goetz describing the research, are available on the Mayo Clinic News Blog http://newsblog.mayoclinic.org/2008/12/11/gene-testing-may-be-key-for-treating-some-women-with-breast-cancer/, with password: sabcs08g.

The latest findings will be presented today at the Cancer Therapy & Research Center-American Association for Cancer Research (CTRC-AACR) 31st annual San Antonio Breast Cancer Symposium.

Tamoxifen, approved by the Food and Drug Administration (FDA) to both prevent development of estrogen-receptor-positive (ER+) breast cancer and as a therapy to stop ER+ breast cancer from coming back, is a "pro-drug"; it must be metabolized in the liver to become active. Mayo researchers had previously discovered that the drug is less effective in postmenopausal breast cancer patients who had a deficiency in the CYP2D6 gene, which is key for activating tamoxifen and many other drugs. However, until now, testing for the gene has not been done routinely at most medical centers.

"These new results validate our earlier findings," says the study's lead investigator, Matthew Goetz, M.D., an assistant professor of oncology and pharmacology at Mayo Clinic, "and strongly suggest that going forward, postmenopausal patients being considered for tamoxifen therapy should be tested for CYP2D6 before beginning therapy."

The research teams examined DNA from a subset of postmenopausal women treated in the ABCSG-8 study, which previously randomized nearly 3,900 women whose ER+ breast cancer had been surgically treated. One group was randomized to five years of tamoxifen therapy, and the other randomized to tamoxifen for two years followed by three years of anastrozole, an aromatase inhibitor. The initial results of ABCSG-8, reported in 2005, concluded that women who switched to anastrozole had a 40 percent reduced risk of breast cancer recurrence compared to staying on tamoxifen.

The aim of the new study was to determine whether CYP2D6 genetic variation would identify a subgroup of patients at higher risk of recurrence within the context of the ABCSG-8 trial. "Among the patients randomized to tamoxifen, poor metabolizers had a 3.8-fold increase in risk of developing breast cancer recurrence than extensive metabolizers across the five-year span," said Michael Gnant, M.D., professor of Surgery at the Medical University of Vienna, Austria, and president of ABCSG. "That is the key message coming out of this great collaboration between the Mayo Clinic team and the Austrian Breast and Colorectal Cancer Study Group."

However, the researchers also demonstrated that among patients who switched to anastrozole, there was no increased risk of breast cancer recurrence for CYP2D6 poor metabolizers in years three to five. The benefit of switching to anastrozole, says Dr. Goetz, may be most pronounced in the group of patients with deficient CYP2D6 metabolism. "Poor metabolizers who were fortunate to not develop breast cancer recurrence in the first two years of tamoxifen appear to be rescued by anastrozole," he says.

The findings reported by Mayo and ABCSG highlight the emerging science of pharmacogenomics. Researchers in this field are studying whether genetic differences in how patients metabolize or process drugs can be used to individualize therapy.

Additionally, in collaboration with bioTheranostics (a molecular diagnostics testing firm), the researchers examined whether a tumor-based test, HOXB13: IL17BR gene expression ratio, and a 5-gene molecular grade index were prognostic markers of distant breast cancer recurrence. Dr. Goetz and his colleagues confirmed that high expression of both HOXB13:IL17BR and molecular grade index, found in 25 percent of the tumors, led to a nearly threefold higher risk of recurrence elsewhere in the body compared to patients whose tumors were considered to be low risk according to these gene markers.

These findings suggest that the combined index will identify patients with early stage breast cancer who haveith a higher risk of distant metastases when treated only with hormonal therapy, the researchers say.


'/>"/>

Contact: Karl Oestreich
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
Source:Eurekalert

Related biology news :

1. New book helps medical students master clinical skills
2. Biochemistry of human physiology in health and disease is focus of updated clinical text
3. Self-assembling nano-fiber gel delivers high concentrations of clinically approved drugs
4. A new journal where molecular biology meets clinical research
5. Prosthetic vein valve designed to direct blood flow shows promising pre-clinical results
6. Clinical trial for new tuberculosis vaccine
7. JDRF-funded clinical trial demonstrates continuous glucose monitoring improves blood sugar control
8. Building bridges between the clinic and the laboratory
9. New study spotlights National Institutes of Health grant outcomes for clinical research
10. NCI grant launches clinical trials for colon cancer screening
11. Florida researchers receive JDRF Excellence in Clinical Research Award
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/4/2017)... 4, 2017   EyeLock LLC , a leader ... United States Patent and Trademark Office (USPTO) has issued ... linking of an iris image with a face image ... the company,s 45 th issued patent. ... timely given the multi-modal biometric capabilities that have recently ...
(Date:3/29/2017)... CHICAGO , March 29, 2017  higi, the ... ecosystem in North America , today ... Partners and the acquisition of EveryMove. The new investment ... extensive set of tools to transform population health activities ... and lifestyle data. higi collects and secures ...
(Date:3/23/2017)... March 23, 2017 The report "Gesture Recognition and Touchless ... and Geography - Global Forecast to 2022", published by MarketsandMarkets, the market is ... of 29.63% between 2017 and 2022. Continue Reading ... ... ...
Breaking Biology News(10 mins):
(Date:4/21/2017)... ... 2017 , ... Frederick Innovative Technology Center, Inc. (FITCI), a ... recently earned a $77,518 grant from the Rural Maryland Council (RMC) to support ... Frederick’s first incubator. A non-profit corporation, FITCI is a public-private partnership of the ...
(Date:4/20/2017)... -- Eli Lilly and Company (NYSE: LLY ) ... prevention of migraine at the American Academy of Neurology ... 2017, in Boston . ... safety and patient outcomes data for galcanezumab in patients ... monthly migraine headache days among patients with episodic migraine. ...
(Date:4/20/2017)... ... 20, 2017 , ... NetDimensions appoints Bill Mastin, a learning technology veteran, as ... experience in the learning technologies industry, Mastin joins NetDimensions from the New York office ... (LTG). At LEO, Mastin served as SVP of the North America offices and prior ...
(Date:4/20/2017)... (PRWEB) , ... April 20, 2017 , ... Parallel6™ ... clinical trials worldwide, announced today that they were named one of the 2017 ... covers the latest developments in the pharmaceutical industry. , “We take pride in honoring ...
Breaking Biology Technology: