Pharmacogenetics of Anastrozole in Postmenopausal Women With Estrogen Receptor-Positive and/or Progesterone Receptor-Positive Stage I, Stage II, or Stage III Breast Cancer
Study Details
Study Description
Brief Summary
RATIONALE: Studying samples of blood in the laboratory from patients with cancer receiving anastrozole may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors learn more about how anastrozole works in the body.
PURPOSE: This research study is looking at the pharmacogenetics of anastrozole in postmenopausal women with estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+) stage I, stage II, or stage III breast cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
OBJECTIVES:
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To evaluate the association of intragenic haplotypes in genes encoding proteins involved in anastrozole metabolism pathways with anastrozole steady state plasma levels in postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive stage I, II, or III breast cancer.
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To evaluate the association of intragenic haplotypes in genes that encode proteins involved in pathways for estrogen synthesis, metabolism, and transport and in genes involved in anastrozole metabolism with the pharmacodynamic (PD) effects of anastrozole therapy, as measured by changes (before vs after drug therapy) in plasma levels of estradiol, estrone, estrone sulfate, testosterone, and androstenedione in these patients.
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To evaluate the association of intragenic haplotypes described above with the PD effects of anastrozole therapy, as measured by changes in breast density and bone mineral density before and at 1 year after drug therapy.
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To collect and bank blood samples and mammographic, bone density, and questionnaire data from patients enrolled on CAN-NCIC-MA27 and randomized to receive exemestane.
OUTLINE: This is a multicenter study. Patients are stratified according to prior tamoxifen use (yes vs no).
Blood samples are obtained for pharmacogenetic studies at baseline, at 6-12 weeks, and then at 1 year. Samples are analyzed for plasma anastrozole concentrations via high-performance liquid chromatography; genotyping for htSNPs via PCR; plasma levels of estradiol, estrone, estrone sulfate, testosterone, and androstenedione via gas chromatographic negative chemical ionization tandem mass spectrometry and liquid chromatographic electrospray tandem mass spectrometry.
Mammograms are obtained at baseline (i.e., within the past 6 months) and at 1 year to assess breast density. Patients with bilateral disease, bilateral breast augmentation, or bilateral mastectomy do not participate in this portion of the study.
Patients at the Mayo Clinic Cancer Center Rochester site also undergo bone mineral density measurement via dual x-ray absorptiometry at baseline and at 1 year. Metabolic markers of bone formation and resorption are also assessed in the Mayo Clinic patients.
Blood samples and mammographic, bone mineral density, and questionnaire data collected from patients randomized to receive exemestane on CAN-NCIC-MA27 are stored for future studies.
Patients complete a questionnaire at baseline, at 6-12 weeks, and at 1 year.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Anastrozole Blood draws for baseline and six to twelve weeks. |
Genetic: Single nucleotide polymorphism (SNP)
Evaluating SNP association with traits.
Other: high performance liquid chromatography
analysis of plasma concentrations of drugs
Other: measurements by DXA
determine bone mineral density (BMD)
Other: questionnaire administration
determine attitude changes
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| Exemestane Blood draws for baseline and six to twelve weeks |
Genetic: Single nucleotide polymorphism (SNP)
Evaluating SNP association with traits.
Other: high performance liquid chromatography
analysis of plasma concentrations of drugs
Other: measurements by DXA
determine bone mineral density (BMD)
Other: questionnaire administration
determine attitude changes
|
Outcome Measures
Primary Outcome Measures
- Association of single nucleotide polymorphisms with specific quantitative traits (i.e., hormone levels, breast density, and bone mineral density) [4 years]
- Association of haplotype with traits [4 years]
Secondary Outcome Measures
- Association of genomic pathways with traits [4 years]
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Diagnosis of breast cancer
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Stage I, II, or III disease
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Resected disease
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Planning to undergo treatment with anastrozole at the clinically approved dose of 1 mg/day OR Mayo Clinic Cancer Center Rochester patient who will be enrolled on or has been enrolled on CAN-NCIC-MA27 and has not started taking the study medication (anastrozole or exemestane)
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Hormone receptor status:
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Estrogen receptor-positive and/or progesterone receptor-positive primary tumor
PATIENT CHARACTERISTICS:
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Female
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Postmenopausal
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Able to complete questionnaires alone or with assistance
PRIOR CONCURRENT THERAPY:
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More than 6 months since prior endocrine therapy, except tamoxifen
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No other prior aromatase inhibitors (e.g., letrozole or exemestane)
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No prior ovarian function suppression with surgery or radiotherapy, ovarian ablation, or luteinizing hormone-releasing hormone analogues (e.g., goserelin) as treatment for cancer
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic in Arizona | Scottsdale | Arizona | United States | 85259-5499 |
| 2 | Mayo Clinic in Florida | Jacksonville | Florida | United States | 32224 |
| 3 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 4 | M. D. Anderson Cancer Center at University of Texas | Houston | Texas | United States | 77030-4009 |
Sponsors and Collaborators
- Mayo Clinic
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: James N. Ingle, MD, Mayo Clinic
- Principal Investigator: Edith A. Perez, MD, Mayo Clinic
- Principal Investigator: Donald W. Northfelt, MD, FACP, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000583001
- MC0532
- 999-05
- NCT00366054