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 Overview
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Brief Summary
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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
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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.

Official Title
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Pharmacogenetics of Aromatase Inhibitors

Conditions
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Breast Cancer

Intervention / Treatment
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* Genetic: Single nucleotide polymorphism (SNP)
* Other: high performance liquid chromatography
* Other: measurements by DXA
* Other: questionnaire administration


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of breast cancer Stage I, II, or III disease Resected disease 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) Hormone receptor status: Estrogen receptor-positive and/or progesterone receptor-positive primary tumor PATIENT CHARACTERISTICS: Female Postmenopausal Able to complete questionnaires alone or with assistance PRIOR CONCURRENT THERAPY: More than 6 months since prior endocrine therapy, except tamoxifen No other prior aromatase inhibitors (e.g., letrozole or exemestane) No prior ovarian function suppression with surgery or radiotherapy, ovarian ablation, or luteinizing hormone-releasing hormone analogues (e.g., goserelin) as treatment for cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Anastrozole<br>Blood draws for baseline and six to twelve weeks. | Genetic: Single nucleotide polymorphism (SNP)<br>* Evaluating SNP association with traits.<br>Other: high performance liquid chromatography<br>* analysis of plasma concentrations of drugs<br>Other: measurements by DXA<br>* determine bone mineral density (BMD)<br>Other: questionnaire administration<br>* determine attitude changes<br>|
| Exemestane<br>Blood draws for baseline and six to twelve weeks | Genetic: Single nucleotide polymorphism (SNP)<br>* Evaluating SNP association with traits.<br>Other: high performance liquid chromatography<br>* analysis of plasma concentrations of drugs<br>Other: measurements by DXA<br>* determine bone mineral density (BMD)<br>Other: questionnaire administration<br>* determine attitude changes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of genomic pathways with traits |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer