Pharmacogenetics of Anastrozole in Postmenopausal Women With Estrogen Receptor-Positive and/or Progesterone Receptor-Positive Stage I, Stage II, or Stage III Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Genetic: Single nucleotide polymorphism (SNP)Other: high performance liquid chromatographyOther: measurements by DXAOther: questionnaire administration
- Registration Number
- NCT00283608
- Lead Sponsor
- Mayo Clinic
- 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.
- Detailed Description
OBJECTIVES:
* 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.
* 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.
* 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.
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 1000
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Anastrozole Single nucleotide polymorphism (SNP) Blood draws for baseline and six to twelve weeks. Exemestane measurements by DXA Blood draws for baseline and six to twelve weeks Anastrozole high performance liquid chromatography Blood draws for baseline and six to twelve weeks. Anastrozole measurements by DXA Blood draws for baseline and six to twelve weeks. Exemestane high performance liquid chromatography Blood draws for baseline and six to twelve weeks Exemestane Single nucleotide polymorphism (SNP) Blood draws for baseline and six to twelve weeks Anastrozole questionnaire administration Blood draws for baseline and six to twelve weeks. Exemestane questionnaire administration Blood draws for baseline and six to twelve weeks
- Primary Outcome Measures
Name Time Method 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
Name Time Method Association of genomic pathways with traits 4 years
Trial Locations
- Locations (4)
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
M. D. Anderson Cancer Center at University of Texas
🇺🇸Houston, Texas, United States