Women with an allele for the CYP2D6 enzyme that results in lowered enzyme activity have almost double the risk for recurrent breast cancer when given five-year tamoxifen therapy, according to an article in the December 20 issue of the Journal of Clinical Oncology.

The study, led by American researchers Matthew Goetz, MD, and James Rae, PhD, tested the most common genetic variant responsible for lowering CYP2D6 enzyme activity, and found that women with this genetic variant were almost twice as likely to see their breast cancer return. Up to 10 percent of women inherit this genetic trait.

"Our group has shown that CYP2D6 is responsible for activating tamoxifen to a metabolite called endoxifen that is nearly 100 times more potent as an anti-estrogen than tamoxifen itself,” said Rae, research assistant professor of internal medicine. “Our study suggests that women who inherit a genetic variant in the CYP2D6 gene appear to be at higher risk of relapse when treated with five years of tamoxifen."

The same research group found that the selective serotonin reuptake inhibitor Paxil can prevent tamoxifen from being activated, whereas another drug of the same antidepressant class, Effexor, does not. These drugs are often used to treat hot flashes, a common side effect of tamoxifen.

In the current study of 256 women with breast cancer, researchers also found that women with the CYP2D6 variant were less likely to have hot flashes. Any hot flashes among this group tended to be less severe, suggesting that this side effect could predict the presence of the gene variation.