In 2007 nearly 180,000 women were diagnosed with breast cancer and 40,000 died from it.  Two-thirds of these breast cancers require estrogen, the naturally occurring female sex hormone, to grow and spread – these are known as ER+ (estrogen receptor positive) cancers. Tamoxifen, a drug that blocks the effects of estrogen in breast tissue, can be very effective in treating these cancers and preventing their recurrence. 

Unfortunately, 35% of ER+ breast cancer patients fail tamoxifen treatment. However recent advances in research may make it possible to reduce the failure rate of tamoxifen treatment to less than 10% by using a simple DNA test and carefully managing other medicines a patient is taking. This could greatly improve treatment outcomes for many of the 500,000 women currently taking tamoxifen.

Before tamoxifen can be effective it has to be metabolized and converted to endoxifen, which is 30 to 100 times more potent than tamoxifen itself. The conversion of tamoxifen to endoxifen is carried out in the liver by an enzyme called CYP2D6. We now know that some women do not have the CYP2D6 because of inherited changes to their DNA. These patioents do not respond well to tamoxifen, and are twice as likely to see their breast cancer return.

Another reason that causes tamoxifen failure for many patients is the lack of ability to convert tamoxifen to endoxifen because of other medicines they are taking “Hot flashes,” for example, is a common side effect of tamoxifen and is often treated with antidepressants. Researchers have found that these and many other medicines reduce the ability of the CYP2D6 enzyme to complete the conversion of tamoxifen to endoxifen. Women with already lowered levels of CYP2D6 are most affected.
Now a simple DNA test available from Genelex (a licensed medical laboratory) can determine a woman’s ability to produce CYP2D6. Included with the test is a software program, GeneMedRx, used to interpret the DNA test results within the framework of all of the medicines a patient is taking. This vital information helps to identify patients who are at risk to fail tamoxifen treatment, and gives doctors a tool to make better treatment choices for each and everyone of their breast cancer patients.

Reprinted from, Research for A Cure, Volume 8 Number 1, National Foundation for Cancer Research, Spring 2008.

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