Research Study Summary
ECOG E3108 Phase II Prospective Study of CYP2D6 Activity in Patients With Metastatic or Recurrent Breast Cancer Treated With Tamoxifen Citrate
WHY IS THIS STUDY BEING DONE?
For tamoxifen, this process of drug metabolism occurs in the liver. To break down tamoxifen into its metabolites, the liver uses several proteins called enzymes. The enzymes work by breaking down tamoxifen into metabolites that your body can easily get rid of. One of the enzymes that is very important in breaking down tamoxifen is called CYP2D6. The level of the enzyme CYP2D6 differs from person to person. Some individuals have high levels of CYP2D6 and metabolize tamoxifen quickly, and we call these individuals "extensive metabolizers", and some individuals lack the enzyme CYP2D6 altogether, and metabolize down tamoxifen very slowly; we call these individuals poor metabolizers. Most people break down tamoxifen somewhere in between these two groups and are called "intermediate metabolizers".
Some research on tamoxifen metabolism suggests that people who are poor metabolizers, and perhaps those who intermediate metabolizers, may not have as much benefit from tamoxifen compared to the extensive metabolizers. This can be due to the fact that when tamoxifen is broken down into its metabolites, some of those metabolites might be helpful in treating the cancer. However, we need more information to look at the benefit of tamoxifen in people who metabolize tamoxifen differently and we hope this study will help us to answer this question.
The purpose of this study is to determine the level of the enzyme CYP2D6 in all of the participants in the study, and then to compare the blood levels of tamoxifen and its metabolites in extensive metabolizers and poor metabolizers. You are being asked to take part because you have breast cancer that has spread to other parts of the body (metastatic breast cancer) and you and your doctor have decided that tamoxifen is an appropriate treatment for you.
Patient Inclusion Criteria:
- Age >18 years
- Histologically confirmed adenocarcinoma of the breast
- Stage III (locally advanced), metastatic, or recurrent disease
- Deemed not resectable
- Estrogen-receptor and/or progesterone-receptor positive disease
- Receptor status is based on most recent results
- Receptor testing on metastatic disease is not required
- Measurable or non-measurable disease
- History of CNS metastasis allowed provided it has been treated (surgery, radiotherapy, or radiosurgery) within the past 4 weeks and does not require medications to control symptoms
- No known leptomeningeal disease allowed
Patient Exclusion Criteria:
Patients may not initiate bisphosphonate therapy while receiving treatment on this study. Patients who have begun receiving bisphosphonate therapy prior to registration may continue at the same intervals used prior to study registration.
Patients must be disease-free of prior invasive malignancies for > 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
Patients must not suffer from medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, or assessment of response or anticipated toxicities.
Patients must not take the following medications that are strong to moderate inhibitors of CYP2D6 and may alter tamoxifen metabolism: paroxetine (Paxil), fluoxetine (Prozac), buproprion (Wellbutrin) and quindine (Cardioquin) within 2 weeks of registration.
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