Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Gene variation affects tamoxifen’s benefit for breast cancer


Women with genetic variant were more likely to see their cancer return

One of the most commonly prescribed drugs for breast cancer, tamoxifen, may not be as effective for women who inherit a common genetic variation, according to researchers at the University of Michigan and the Mayo Clinic. The genetic variation affects the level of a crucial enzyme that activates tamoxifen to fight breast cancer.

The study, co-led by researcher James Rae, Ph.D., at the University of Michigan Comprehensive Cancer Center and Matthew Goetz, M.D., an oncologist at the Mayo Clinic, tested the most common genetic variant responsible for lowering the CYP2D6 enzyme, and found that women with this genetic variant were almost twice as likely to see their breast cancer return. Up to 10 percent of women inherit this genetic trait.

Their findings are published in the Dec. 20 issue of The Journal of Clinical Oncology.

"Our group has shown that CYP2D6 is responsible for activating tamoxifen to a metabolite called endoxifen that is nearly 100 times more potent as an anti-estrogen than tamoxifen itself," says Rae, research assistant professor of internal medicine at the U-M Medical School. "Our study suggests that women who inherit a genetic variant in the CYP2D6 gene appear to be at higher risk of relapse when treated with five years of tamoxifen."

Researchers at the U-M Comprehensive Cancer Center were among the group to discover CYP2D6 metabolizes tamoxifen, and they are leading ongoing work looking at how genetic differences affect women’s response to tamoxifen. Their research has also found the antidepressant drug Paxil can prevent tamoxifen from being activated, while the antidepressant drug Effexor does not. These drugs, selective serotonin reuptake inhibitors or SSRI’s, are often used to treat hot flashes, a common side effect of tamoxifen.

In this current study of 256 women with breast cancer, researchers also found that women with the CYP2D6 variant were less likely to have hot flashes. Any hot flashes among this group tended to be less severe, suggesting that this side effect could predict the gene variation.

Further studies are needed, but researchers hope one day this finding may lead to a genetic test that could help doctors determine which women are most likely to benefit from tamoxifen. This type of test is not currently offered clinically.

Rae and Daniel F. Hayes, M.D., director of breast oncology at the U-M Comprehensive Cancer Center, are part of the Pharmacogenetics Research Network, a multidisciplinary research group conducting a prospective clinical trial to confirm whether genetic testing can be used to identify patients likely to respond to endocrine therapy, including tamoxifen. This group is led by David A Flockhart, M.D., Ph.D. at Indiana University School of Medicine.

More than 210,000 women in the United States will develop breast cancer. Approximately 70 percent of these cancers are fueled by estrogen, many of which are treated with tamoxifen, a drug designed to block the effects of estrogen in breast tissue. The findings from this trial were derived from a large North Central Cancer Treatment Group study in which women were treated with tamoxifen, a pill that is taken daily, for a total of five years.

Additional authors included the following researchers from the Mayo Clinic Cancer Center: Vera Suman, Ph.D.; Stephanie Safgren; Matthew Ames, Ph.D.; Daniel Visscher, M.D.; Carol Reynolds, M.D.; Fergus Couch, Ph.D.; Wilma Lingle, Ph.D.; and James Ingle, M.D., in Rochester, Minn.; and Edith Perez, M.D., in Jacksonville, Fla.; David Flockhart, M.D., Ph.D., and Zeruesenay Desta, Ph.D., both from Indiana University are also co-authors.

Nicole Fawcett | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Molecular doorstop could be key to new tuberculosis drugs
20.03.2018 | Rockefeller University

nachricht Modified biomaterials self-assemble on temperature cues
20.03.2018 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Physicists made crystal lattice from polaritons

20.03.2018 | Physics and Astronomy

Mars' oceans formed early, possibly aided by massive volcanic eruptions

20.03.2018 | Physics and Astronomy

Thawing permafrost produces more methane than expected

20.03.2018 | Earth Sciences

Science & Research
Overview of more VideoLinks >>>