NCT00815555

CYP2D6 Genotyping by AmpliChipTM CYP450 for Tamoxifen-Treated Breast Cancer Patients

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 500 (estimated)
• Sponsor: Assaf-Harofeh Medical Center · Other Government
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The aim of the study is to examine whether tamoxifen-treated Israeli breast cancer patients who are CYP2D6 poor metabolizers (CYP2D6\*4/\*4 genotype) are at higher cancer relapse risk during 2.5-5-year follow-up period from initial diagnosis and primary treatment.

Detailed description

Tamoxifen, the first-line drug for preventing breast cancer relapse, is typically prescribed for a 5-year follow-up period after diagnosis and primary treatment of estrogen receptor-positive breast cancer. Recent studies show that tamoxifen is only a pro-drug, while its major active metabolite, endoxifen, is formed in vitro by the liver enzyme CYP2D6. Preliminary observations from the US and Italy have suggested that tamoxifen is less efficacious for cancer relapse prevention in patients with deficient CYP2D6 activities. The FDA is currently reviewing the new data and is likely to modify the tamoxifen label accordingly. It was suggested that an aromatase inhibitor drug such as letrozole might be more beneficial for these patients. The proposed study would retrospectively test CYP2D6 genotypes in 200 - 300 estrogen receptor (ER) positive breast cancer patients who are treated with tamoxifen post-operatively. Blood collected with informed consent would be used for examining the patients CYP2D6 genotype, and identifying those who are CYP2D6 poor metabolizers (CYP2D6\*4/\*4 genotype), and for measurement of endoxifen blood level in those women who are on the drug. AmpliChipTM CYP450 is a microarray chip which contains millions of tiny DNA molecules, providing comprehensive coverage of gene variations that play a role in the metabolism of approximately 25% of all prescription drugs. The AmpliChipTM CYP450 test is intended to be an aid for physicians in individualizing treatment doses for patients receiving therapeutics metabolized through these enzymes. The clinical data collected would examine if these individuals, as well as those treated with CYP2D6 inhibiting drugs such as paroxetine and fluoxetine, have higher cancer relapse rates. The study, combined with similar findings from other countries, and possibly integrated later on with an international network study, would be imperative for modifying treatment recommendations for breast cancer therapy. Specifically, if the US and Italian findings are confirmed, it might be advisable to switch the 5-year follow-up treatment for breast cancer patients with ER positive primary tumors who are CYP2D6 poor metabolizers from tamoxifen to an aromatase inhibitor drug such as letrozole.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
OTHER	There is no intervention - this is an observational study

Timeline

• Start date: 2008-12-01
• Primary completion: 2011-12-01
• First posted: 2008-12-30
• Last updated: 2008-12-30

Locations

1 site across 1 country: Israel