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

May 13, 2011 updated by: Mayo Clinic

Pharmacogenetics of Aromatase Inhibitors

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Anticipated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259-5499
        • Mayo Clinic in Arizona
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic in Florida
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Texas
      • Houston, Texas, United States, 77030-4009
        • M. D. Anderson Cancer Center at University of Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

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)

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Association of single nucleotide polymorphisms with specific quantitative traits (i.e., hormone levels, breast density, and bone mineral density)
Time Frame: 4 years
4 years
Association of haplotype with traits
Time Frame: 4 years
4 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Association of genomic pathways with traits
Time Frame: 4 years
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2005

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

March 1, 2010

Study Registration Dates

First Submitted

January 27, 2006

First Submitted That Met QC Criteria

January 27, 2006

First Posted (Estimate)

January 30, 2006

Study Record Updates

Last Update Posted (Estimate)

May 16, 2011

Last Update Submitted That Met QC Criteria

May 13, 2011

Last Verified

May 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000583001
  • MC0532 (Other Identifier: Mayo Clinic Cancer Center)
  • 999-05 (Other Identifier: Mayo Clinic IRB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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