If you go to PubMed and enter in Tamoxifen and 2D6, the research speaks clearly. A good synopisis from the Genelex Fall newsletter is included below. The question is why is this testing still rarely ordered for breast cancer patients? What are your thoughts?

According to the American Cancer Society, one in eight women in the United States will develop breast cancer in her lifetime and 1 in 33 will die from it. Every year, nearly 180,000 additional women are diagnosed with breast cancer and more than 40,000 die. It is the second leading cause of cancer death in women, after lung cancer.

Genetic testing may hold the key to improving these odds. About two-thirds of newly diagnosed breast cancer patients are ER (estrogen-receptor) positive and are candidates for hormonal therapy. Tamoxifen is a likely choice of treatment in these cases but one third of breast cancer patients currently fail tamoxifen treatment. Genetic testing identifies patients that are at risk for failure.This vital information gives medical providers a tool to better manage treatment and drug regimens.

Tamoxifen is converted to the active compound endoxifen in the liver by an enzyme called CYP2D6 (CytochromeP450 2D6). Endoxifen is 30-100 times more effective than tamoxifen. A DNA test can determine a person’s genetic ability to create levels of this enzyme. The more of the 2D6 enzyme a woman has the better she can absorb tamoxifen and convert it, thereby avoiding relapse.

About 7-10% of women are CYP2D6 poor metabolizers with absent or greatly reduced levels of this enzyme. Another 35% are intermediate metabolizers that have slightly lowered levels of the enzyme. Intermediate metabolizers and even normal metabolizers can also be at an increased risk of relapse when certain other medications are taken at the same time.A common side effect of tamoxifen treatment is hot flashes, commonly treated with anti-depressants such as Paxil. A few years ago several doctors wondered if the anti-depressants were making Tamoxifen less effective. That is, were they preventing the enzyme 2D6 from doing its job?

The answer is yes. Many anti-depressants such as Paxil reduce the ability of the 2D6 enzyme to work, so women taking the medication - espcially those that were poor or intermediate metabolizers of 2D6 – were not getting the needed benefit from tamoxifen.

This suggests that widespread genetic testing and careful analysis of overall drug regimens could result in successful outcomes for many of the 35% of ER positive breast cancer patients who currently fail tamoxifen treatment. With more than 500,000 women currently taking tamoxifen, this research has wide-reaching implications.

“I hope that this technology is quickly adopted in the medical community.This is a simple and fairly inexpensive test that can help physicians improve breast cancer survival rates,” stated Howard Coleman, Genelex CEO.

Who Should Be Tested?

The CYP2D6 test for tamoxifen is considered appropriate for postmenopausal women who are currently taking or considering tamoxifen to prevent the recurrence of breast cancer. It is especially important if the patient is also taking or considering co-administration with anti-depressants.