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Tamoxifen Ineffective In Presence Of Genetic Variation in Breast Cancer

Researchers at the University of Michigan and the Mayo Clinic say that the flagship breast cancer drug, tamoxifen might not be very effective in women who inherit a common genetic variation. //

This particular variant gene has the ability to influence the levels of a crucial enzyme that is vital to activate tamoxifen against breast cancer. The study which was conducted by James Rae, Ph.D., at the University of Michigan Comprehensive Cancer Center and Matthew Goetz, M.D., an oncologist at the Mayo Clinic, found that women who carried a variant of this gene had low levels of the CYP2D6 enzyme. This in turn predisposed for a relapse of the breast cancer. CYP2D6 enzyme is responsible for the metabolization of tamoxifen and plays a crucial role in triggering off the drug's activity against the cancer cells. The UM researchers were also a part of the team that found the adverse affect of the antidepressant drug Paxil on tamoxifen. In the present study, the researchers looked at the enzymatic profile of 256 women with breast cancer. They also found that women who carry the genetic variant do not have intense hot flashes. The researches added that additional tests are needed to confirm these variations, but are hopeful of a clinical test to determine which women can reap the maximum benefit from tamoxifen. "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 lead researcher Dr Rae. '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 study is detailed in the December 20 issue of The Journal of Clinical Oncology.
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