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                       CYP2D6 testing and tamoxifen

  Source BioScience now offers the Roche AmpliChip^® CYP450 test, which uses novel DNA microarray technology and a small blood sample to identify the metaboliser group to which an individual belongs. Recent data suggest this knowledge is likely to be of great value in individualising patient treatment with adjuvant hormonal therapy.

  Individuals can be shown to fall into 4 categories according to their ability to metabolise a wide range of drugs. Such differences arise because of small genetic variations in the CYP2D6 gene. This gene codes for an enzyme, CYP2D6, which is responsible for drug metabolism. Of particular interest to oncologists and breast surgeons is that tamoxifen is one of the drugs metabolised by this enzyme, which converts tamoxifen, a pro-drug, to its active form "endoxifen".

 Compelling data, recently published in peer-reviewed journals and based upon the largest studies yet to take place, indicate that breast cancer patients with decreased CYP2D6 activity have worse event-free and disease-free survival outcomes with tamoxifen treatment (1,2). These studies suggest that patients predicted to have low CYP2D6 levels will not benefit from tamoxifen treatment, and should therefore be considered for alternative endocrine therapy.  

  Certain drugs, such as SSRIs, which are sometimes used concurrently with tamoxifen, may also inhibit CYP2D6 and hence affect tamoxifen metabolism.

 There is some evidence that this test may be useful for the following patients:-

 1)      Those already using Aromotase Inhibitors who are experiencing severe bone pain or other side effects, where the physician may be considering switching to tamoxifen. If  the patient is shown to be a high metaboliser then tamoxifen is likely to be effective

2)      Patient who are using tamoxifen and experiencing no side effects. This might be because they are poor metabolisers and the drug is not being effectively metabolised.

3)      New patients being considered for tamoxifen.

 

References:

1. Schroth W et al (2009) The Breast 18, supp 1, S34
2. 2.      Goetz M (2008) San Antonio Breast Cancer Symposium, December 2008 (Abstract).