More Clinical Evidence that Metabolism of Tamoxifen Effects Recurrence

More evidence out today that women taking tamoxifen for hormone responsive breast cancer should determine if they are good metabolizers of the drug.  Poor metabolizers have a significantly higher rate of recurrence, according to a study published online today in the Journal of the American Medical Association (JAMA).

Tamoxifen by itself does not inhibit the growth of tumor cells.  It must be converted to an active form, which requires an enzyme called CYP2D6.  The problem is that there is genetic variation in CYP2D6 among different women.  Some women are completely missing the genetic code needed to make the enzyme, while others have just half of the genetic code needed.

Researchers from Germany and the US analyzed tumor tissues or blood samples from 1325 breast cancer patients receiving tamoxifen.  By looking for the genetic code for CYP2D6, or DNA genotype in the samples, the patients were grouped into high metabolizers (n=609), intermediate metabolizers (n=637) and poor metabolizers (n=79).

After nine years of follow-up, recurrence rates were 14.9% for high metabolizers, 20.9% for intermediate metabolizers, and 29.0% for poor metabolizers.  The recurrence rates were statistically significantly different between high metabolizers, and both intermediate and poor metabolizers.  However, there was not a significant difference in overall survival.  This doesn’t mean that there isn’t a difference in overall survival, but that this study may not have gone on long enough or the size of the study may not be big enough to show the difference statistically.

Anyone have experience on CYP2D6 testing and insurance coverage?  Would love to hear about your experiences!  The evidence certainly seems strong enough now for those of us taking tamoxifen to be asking our oncologists about testing.

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  • Joy Simha  On October 8, 2009 at 7:14 am

    This study looked at women taking Tamoxifen in the adjuvent setting. What about the Metastatic Setting? This also leads me to believe that Metastatic Patients who choose Tamoxifen as a first line of defense should first undergo CYP2D6 testing before beginning treatment. I don’t even think that is happening everywhere.

  • rebeany  On October 21, 2009 at 9:30 pm

    i live in new york city and my oncologist is at st. vincent’s cancer center. i have had the test – i know i do metabolize the tamoxifen but now have asked for the number results to try to understand this better. i was pre-menapausal and was kicked into menapause after 1 chemo…that was almost-4 years ago. my oncologist is pressuring me to start on an aromatase and i’m not convinced that the side effects are worth it. i also had a oncotype test early on and my probably recurrance rate was over the halfway mark – so aggressive enough to be worrisome.

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