Certain Gene May Hamper Drug Action
November 16, 2006 
Yahoo! Health: Breast Cancer News
Women with breast cancer are often prescribed tamoxifen to reduce the chances of their cancer coming back. Women with a certain type of gene, however, may not get as much benefit from this therapy as others do. The drug label for tamoxifen should disclose that information, a federal panel recommended recently.
The panel, an advisory group to the Food and Drug Administration (FDA), was considering the relationship between tamoxifen and CYP2D6, a gene that helps break down the drug in the body so it can work.
Everyone has the CYP2D6 gene. But several small studies suggest women with a certain variation of CYP2D6 aren't able to metabolize tamoxifen completely, making the drug less effective for them.
The drug label for tamoxifen should be updated to include this information, the panel recommended. The FDA will be making a decision about the panel's recommendations in the coming months.
Tamoxifen's effectiveness can also be weakened by interaction with some members of a class of drugs called selective serotonin reuptake inhibitors. SSRIs such as fluoxetine (Prozac) and paroxetine (Paxil) are commonly prescribed for depression but have also been shown to relieve the hot flashes that are a common side effect of tamoxifen therapy. In general, women taking these 2 SSRIs are less able to metabolize tamoxifen, and this is especially true if they have the variant type of the CYP2D6 gene. All women taking tamoxifen should let their doctors know if they are also taking one of these SSRI medications.
Should breast cancer patients get tested for the CYP2D6 variant before they start tamoxifen treatment? The advisory panel made no recommendation one way or the other.
But some experts say such testing could be useful, if done under the proper circumstances. Those circumstances would include testing in consultation with a breast cancer doctor and not on one's own, says noted tamoxifen researcher Aman Buzdar, MD, of the University of Texas M.D. Anderson Cancer Center.
Consumers can find genetic tests marketed on the Internet for $300 or so, but an experienced physician needs to be on hand to interpret the results and advise the patient on the next steps, he says.
"It's not something simple which could be done easily by the patient herself," says Buzdar. "Somebody has to counsel her after the results come up as to what are the choices, and there are a number of implications about what needs to be done about treatment and how the disease should be managed."
Done properly, though, testing could help women and their doctors balance the risks and benefits of tamoxifen, Buzdar says. The drug can increase the risk of endometrial cancer, blood clots, and cataracts, and it can cause hot flashes, vaginal discharge, and mood swings.
Such side effects may be justified if tamoxifen is going to reduce a woman's risk of breast cancer recurrence, but they may not be if the woman isn't going to get the full benefit of tamoxifen, says Buzdar, who is deputy chairman and professor of medicine in M.D. Anderson's department of Breast Medical Oncology.
"This is a first step in the direction of individualized therapy," he says, "and we might be able to identify women in which tamoxifen is not appropriate therapy."
Testing is the only way to know if a woman is not processing tamoxifen effectively, Buzdar said. There are no signs or symptoms that would indicate a problem. Between 7% and 10% of breast cancer patients are thought to have the gene variant that makes them process tamoxifen poorly.
Tamoxifen has been used for decades to help keep breast cancer from coming back in women whose cancer cells have estrogen receptors (ER+). It blocks estrogen from affecting these cells, which can help keep tumors from growing. Tamoxifen is used both for women who have not yet been through menopause (premenopausal) and those who are past menopause (postmenopausal).
But there are other options for women who can't process tamoxifen effectively, Buzdar says.
A newer class of drugs called aromatase inhibitors can be given to women who are past menopause, even if they've been using tamoxifen for a couple of years already. Like tamoxifen, these drugs only work for women whose tumors have estrogen receptors. Aromatase inhibitors are generally not used in premenopausal women because these drugs cannot stop the ovaries from producing estrogen.
However, premenopausal women who need a tamoxifen alternative can take drugs to stop their ovaries from producing estrogen, he says.
