Something to Worry About? CYP2D6 and Tamoxifen/Nolvadex Effectiveness

Kevin Knopf, MD Health Guide
  • Tamoxifen (Nolvadex) Effectiveness: Something to worry about?

    Over my morning coffee and one of the three daily newspapers I read I see a note “Panel seeks Cancer-Drug Warning” hot off the AP wire. Here's a link to other outlets that reported on it.

    It turns out that an FDA panel wants to warn women on tamoxifen (nolvadex) that there is a 7% to 10% chance that the drug might not be as effective as thought. The biology is interesting – the liver has a large number of enzymes called cytochorome P 450s that metabolize drugs. One cytochrome involved in tamoxifen metabolism (breaking down tamoxifen to another product) is called CYP2D6. So the blood levels of tamoxifen can be affected by whether a woman has two good copies of CYP2D6 or not.

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    Each of us gets two copies of this gene (one from Mom, one from Dad) that makes this protein, and my understanding was from the paper I had perused by Dan Hayes MD (at U of Michigan) that if a woman has two copies of the variant gene it would make tamoxifen less effective; one good copy/one variant copy or two good copies would not affect the metabolism that much.

    What to do? If you’re on an aromatase inhibitor, no need to worry. Almost all of my postmenopausal breast cancer patients are on an aromatase inhibitor. But aromatase inhibitors won’t work in premenopausal breast cancer patients. There may be a genetic test that checks to see how many “good” copies of CYP2D6 a woman has – stay tuned (I am writing this 1 hour after reading the paper).

    The idea that pharmaceutical agents work differently depending on what genes we have is a fascinating area of cancer research called pharmacogenomics. I'll explore more about pharmacogenomics in future blogs.

    It is also interesting how oncologists and other doctors find out about news this big – were it not for my newspaper I don’t know when it would first come to my attention (I’ll let you know next month!) When I asked my partner if he had heard about it, it was news to him. There are often no “mass broadcasts” of “breaking news” –e.g. nothing on my email yet. So this can create anxiety for patients who might see something before their oncologist does. I think the best approach would be to let the information get absorbed prior to making any decisions about tamoxifen and to seek guidance from your personal oncologist.

Published On: November 29, 2006