Gene Test Can Indicate Whether Tamoxifen Can Fight Breast Cancer

Dec. 17, 2007 — -- 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.