Gene Test Can Indicate Whether Tamoxifen Can Fight Breast Cancer

A test to determine a woman's genetic makeup may predict whether she is likely to benefit from the commonly prescribed breast cancer drug Tamoxifen, according to a study presented at the San Antonio Breast Cancer Symposium, Sunday.

Researchers presented data that revealed women who inherit a common genetic variation that lowers CYP2D6 — a crucial enzyme that activates Tamoxifen to fight breast cancer — are almost twice as likely to have their breast cancer recur. About 10 percent of women inherit this genetic variation.

Tamoxifen is a drug commonly used to treat women with estrogen receptor positive breast cancer. About 75 percent of all breast cancers are estrogen receptor positive, meaning that the cancer cells have receptors, which will respond to hormone therapy.

The drug works by interfering with the hormone estrogen, thereby reducing both breast cancer risk and the chances that breast cancer will return after a woman has been treated. The CYP2D6 enzyme helps metabolize Tamoxifen.

Researchers at the University of Michigan and the Mayo Clinic in Rochester, Minn., genotyped 297 breast cancer patients to determine their levels of CYP2D6 and other estrogen receptor variants. Based on this genotype information, researchers assigned patients a CYP2D6 "score."

The data presented at the symposium revealed that all women with a CYP2D6 score of zero, meaning they had no activity of this enzyme, completed their Tamoxifen treatment. Researchers found that the higher a woman's CYP2D6 score, the less likely she was to complete their Tamoxifen treatment, mainly because of the negative side effects they experienced from the drug.

Tamoxifen causes unpleasant side effects such as hot flashes, night sweats and nausea. But previous research suggests that there is a benefit to the side effects from Tamoxifen — the side effects signal that the drug is working, so the suffering has a big payoff in terms of a much lower cancer risk. This study also suggests that patients most likely to benefit from Tamoxifen are paradoxically the most likely to discontinue their treatment because of the unpleasant side effects.

"The individuals with this genetic variant are more likely to stay on the drug [Tamoxifen], but paradoxically they are less likely to benefit from it," said Dr. James Rae, lead investigator of the study and professor in the department of internal medicine at the University of Michigan. "The reason they stay on it is because they don't experience the side effects associated with it because they're not activating it."

Scientists estimate that more than 40,000 recurrences are prevented worldwide each year because of Tamoxifen. However, Tamoxifen treatment must be continued for five years in order to reap the benefits of the drug in reducing the chances of disease recurrence.

According to a study published in the March 1, 2007 issue of CANCER, a peer-reviewed journal of the American Cancer Society, more than one-third of women prematurely cease their Tamoxifen treatment after 3.5 years.

Researchers reported that about 10.8 percent of patients in the study stopped taking Tamoxifen during the first year of treatment due to side effects, making the discontinuation rate of Tamoxifen treatment about 15 percent for the study group.

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