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

Breast Cancer Clinical Trial

Official title:

Pharmacogenetics of Aromatase Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00283608
• Other study ID #: CDR0000583001
• Secondary ID: MC0532999-05
• Status: Completed
• Phase: N/A
• First received: January 27, 2006
• Last updated: May 13, 2011
• Start date: July 2005
• Est. completion date: March 2010

Study information

• Verified date: May 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00366054

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Genetic:
• Single nucleotide polymorphism (SNP)
Evaluating SNP association with traits.

Other:
• high performance liquid chromatography
analysis of plasma concentrations of drugs
• measurements by DXA
determine bone mineral density (BMD)
• questionnaire administration
determine attitude changes

Locations

Country	Name	City	State
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Ingle JN, Buzdar AU, Schaid DJ, Goetz MP, Batzler A, Robson ME, Northfelt DW, Olson JE, Perez EA, Desta Z, Weintraub RA, Williard CV, Flockhart DA, Weinshilboum RM. Variation in anastrozole metabolism and pharmacodynamics in women with early breast cancer — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association of single nucleotide polymorphisms with specific quantitative traits (i.e., hormone levels, breast density, and bone mineral density)		4 years	No
Primary	Association of haplotype with traits		4 years	No
Secondary	Association of genomic pathways with traits		4 years	No