Know Cancer

forgot password

Pharmacogenetics of Aromatase Inhibitors

18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

Pharmacogenetics of Aromatase Inhibitors


- 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

- 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

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.

Inclusion Criteria


- 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


- Female

- Postmenopausal

- Able to complete questionnaires alone or with assistance


- 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

Type of Study:


Study Design:

Observational Model: Cohort, Time Perspective: Prospective

Outcome Measure:

Association of single nucleotide polymorphisms with specific quantitative traits (i.e., hormone levels, breast density, and bone mineral density)

Outcome Time Frame:

4 years

Safety Issue:


Principal Investigator

James N. Ingle, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Federal Government

Study ID:




Start Date:

July 2005

Completion Date:

March 2010

Related Keywords:

  • Breast Cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • Breast Neoplasms



Mayo Clinic Rochester, Minnesota  55905
M. D. Anderson Cancer Center at University of Texas Houston, Texas  77030-4009
Mayo Clinic in Arizona Scottsdale, Arizona  85259-5404
Mayo Clinic in Florida Jacksonville, Florida  32224