Pharmacogenetics of Anastrozole in Postmenopausal Women With Estrogen Receptor-Positive and/or Progesterone Receptor-Positive Stage I, Stage II, or Stage III Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00283608
First received: January 27, 2006
Last updated: May 13, 2011
Last verified: May 2011
  Purpose

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 Intervention
Breast Cancer
Genetic: Single nucleotide polymorphism (SNP)
Other: high performance liquid chromatography
Other: measurements by DXA
Other: questionnaire administration

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacogenetics of Aromatase Inhibitors

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Association of single nucleotide polymorphisms with specific quantitative traits (i.e., hormone levels, breast density, and bone mineral density) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Association of haplotype with traits [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Association of genomic pathways with traits [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Anastrozole treatment group samples will be used as described for this study, and then will be destroyed.

Exemestane treatment group samples of blood will be stored at Mayo Clinic Rochester.


Estimated Enrollment: 1000
Study Start Date: July 2005
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Diagnosis of breast cancer. Stage I, II, or III 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)

Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00283608

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: James N. Ingle, MD Mayo Clinic
Principal Investigator: Edith A. Perez, MD Mayo Clinic in Florida
Principal Investigator: Donald W. Northfelt, MD, FACP Mayo Clinic in Arizona
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: James N. Ingle, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00283608     History of Changes
Obsolete Identifiers: NCT00366054
Other Study ID Numbers: CDR0000583001, MC0532, 999-05
Study First Received: January 27, 2006
Last Updated: May 13, 2011
Health Authority: United States: Federal Government

Keywords provided by Mayo Clinic:
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Anastrozole
Aromatase Inhibitors
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014