Genes affect benefits of breast cancer drug


The gene for an enzyme called cytochrome P450 2D6 (CYP2D6) influences how well the breast cancer drug tamoxifen works and whether hot flashes are likely to occur, according to a report in the Journal of Clinical Oncology.

Genes affect benefits of breast cancer drug - Monday, January 16, 2006 at 18:05 
NEW YORK (Reuters Health)
Thursday, January 12, 2006

By Will Boggs, MD
"CYP2D6 appears to be critically important for tamoxifen's anti-cancer effect," Dr. Matthew P. Goetz from Mayo Clinic College of Medicine, Rochester, Minnesota told Reuters Health.

Goetz and colleagues previously observed that CYP2D6 is needed to convert tamoxifen into its active form. In this study, the researchers investigated whether common changes in the CYP2D6 gene influenced the outcomes of 223 women treated with tamoxifen as part of their breast cancer therapy.

Women with a gene profile in which CYP2D6's ability to convert tamoxifen to the active form was limited were more likely to experience a recurrence of their breast cancer than were other women. The researchers also found that these "poor metabolizers" experienced little or no hot flashes.

"Although CYP2D6 (gene testing) is already commercially available, at this time we have stated that we would like our data to be confirmed before routinely recommending" such testing, Goetz said.

Assuming the data are confirmed, "there would be little reason to increase the dosage of tamoxifen for CYP2D6 poor-metabolizers, because...there is no evidence that increasing tamoxifen dose will increase" levels of the active form of the drug, Goetz explained.

Conversely, some women have a genetic profile that makes CYP2D6 even better than normal at converting tamoxifen to its active form. For these women, smaller doses of tamoxifen than usually given may be appropriate, he added.

"Our next goal is to look at the effect of medications that inhibit CYP2D6 on the risk of breast cancer relapse," Goetz said. "This is critically important as some very common medications are frequently administered to patients while on tamoxifen to either treat depression or to alleviate tamoxifen-induced hot flashes."

SOURCE: Journal of Clinical Oncology, December 20, 2005.

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