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| Dr. Matthew Goetz is an assistant professor of oncology at Mayo Clinic. He was the lead researcher in the study on tamoxifen and the enzyme 2D6. The study is published in the Journal of Clinical Oncology. (MPR photo/Sea Stachura) |
Rochester, Minn. — You may have never heard of cytochrome 2D6 but it's becoming famous. 2D6 is part of a gene that produces an enzyme. It helps the body metabolize a host of drugs for a number of diseases. In a breast cancer patient 2D6 can help the body metabolize a drug called Tamoxifen.
Dr. Matthew Goetz, an assistant professor of oncology at Mayo Clinic, says that's a common drug given after surgery to prevent the return of estrogen-based cancer. Goetz says one of Tamoxifen's side effects mimics menopause.
"When we administer Tamoxifen we tell women that the most common side effect is hot flashes," Goetz says. "That's because Tamoxifen is an anti-estrogen so that anti-estrogen leads to what we call a phenotype which is hot flashes."
Goetz says doctors often prescribe anti-depressants along with Tamoxifen to alleviate the hot flashes. A few years ago a group of doctors wondered if the anti-depressants were making Tamoxifen less effective. That is, were they preventing the enzyme 2D6 from doing its job?
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This is the first study that shows the potential benefit of using genetic information to predict the outcomes of women based on the metabolism of Tamoxifen.
- Dr. Matthew Goetz
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The answer is yes, because 2D6 not only creates the enzyme that metabolizes Tamoxifen, it converts it. Tamoxifen's converted form, or its metabolite as doctors say, is far more effective in preventing breast cancer.
"The anti-depressant Paxil potently inhibited the production of this metabolite such that women who were chronically taking Tamoxifen had much lower levels of this potent metabolite," Goetz says.
And that's a problem. The more of the 2D6 enzyme a woman has the better she can absorb Tamoxifen and convert it, thereby avoiding relapse.
But what if a woman's genetic code has less cytochrome 2D6 to begin with? That's something Goetz and researchers at the University of Michigan had been wondering about. It could put a woman at higher risk of relapse. That's because the less 2D6 a woman has in her body the less able she is to metabolize Tamoxifen.
So they took DNA from tumor samples of 250 breast cancer survivors. Each of these women had taken Tamoxifen for five years following surgery.
"And then we looked at the most common genetic change that's responsible for lowering the enzyme," Goetz said, "and specifically asked, 'Well, did the women who received Tamoxifen who had that genetic change -- did they do worse than the women who had normal levels of this enzyme?'"
Those women had nearly twice the risk of relapse. And they tended not to have hot flashes, one of Tamoxifen's key side effects. Goetz says that was important, because it was an indication the drug wasn't effective.
Goetz says figuring out a course of treatment for a breast cancer patient depends not only on genetics but age. If a woman can't absorb Tamoxifen and is post-menopausal she has other drug options. Those options are often more successful than Tamoxifen. But Goetz says those drugs are not available for pre-menopausal women.
"And so for these women we may recommend additional therapies such as shutting down the ovaries," Goetz says.
The study still needs to be independently verified, but the laboratory work and the clinical study mirrored each other.
"This is the first study that shows the potential benefit of using genetic information to predict the outcomes of women based on the metabolism of Tamoxifen," Goetz says.
These results are a major score for breast cancer treatment and pharmacogenomics. That's the study of a person's genetic code to determine how she'll respond to a given drug. Goetz says he hopes genetic information will be a regular feature of a patient's medical records.
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