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

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.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Other: There is no intervention - this is an observational study

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.

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

Study Locations

• Israel
  • Zerifin, Israel, 70300
    • Recruiting
    • Clinical Pharmacology Unit - Assaf Harofeh Medical Center
    • Contact: Matitiahu Berkovitch, Prof; Phone Number: 972-57-345152; Email: mberkovitch@asaf.health.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Women diagnosed with receptor positive breast cancer, treated with Tamoxifen

Description

Inclusion Criteria:

• Female
• Age > 18
• Treated with Tamoxifen following diagnosis of breast cancer

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; Women diagnosed with receptor positive breast cancer, treated with Tamoxifen	Other: There is no intervention - this is an observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Tamoxifen efficacy for avoiding breast cancer relapse in relation to CYP2D6 genotype

Secondary Outcome Measures

Outcome Measure
Prevalence of CYP2D6 poor metabolizers genotype in Israeli female population treated with Tamoxifen

Collaborators and Investigators

• Sponsor: Assaf-Harofeh Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: December 28, 2008
• First Submitted That Met QC Criteria: December 29, 2008
• First Posted (Estimate): December 30, 2008

Study Record Updates

• Last Update Posted (Estimate): December 30, 2008
• Last Update Submitted That Met QC Criteria: December 29, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: relapse; receptor positive breast cancer; Tamoxifen treatment; CYP2D6 status
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 135/08