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Breast cancer gene may hinder tamoxifen

Date published: 20/12/2005

Breast cancer drug Tamixofen may not be as effective for women who inherit a common genetic variation of the disease, a study has suggested. A team from the University of Michigan and the Mayo Clinic found that women with the inherited gene change were twice as likely to suffer a relapse if they took tamoxifen. This is because the inherited gene change affects the level of a crucial liver enzyme known as CYP2D6 which activates Tamoxifen, enabling it to fight the cancer.

The study, led by Professor James Rae and Dr Matthew Goetz, said up to ten per cent of women inherit this genetic breast cancer trait. Professor Rae said: "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.

"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."

Tamoxifen is an anti-oestrogen drug which is widely used to treat breast cancer. Developed over 30 years ago, it works by targeting the oestrogen receptors, known as ER-positive, which help breast cancer cells grow.

The doctors also found that women who had the CYP2D6 variant were less likely to have hot flushes and when they did, the flushes were much less severe. Professor Rae says this could be used as an indicator to decide which women would benefit the most from treatment with tamoxifen. The team says the findings, which were published in the Journal of Clinical Oncology, are important as many women were also coprescribed antidepressant drugs to suppress the hot flushes. However, the drugs were also found to make tamoxifen less effective.

They said: "In addition to being at higher risk of relapse, the women with the genetic change also did not develop one of the most common side effects of tamoxifen - hot flashes. "These findings are important, as doctors commonly co-prescribe drugs such as antidepressants for the treatment of hot flashes, and many of these drugs potently inhibit the metabolism of tamoxifen."

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