Trial Information

Pharmacogenetics of Aromatase Inhibitors

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.