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Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles

18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles

Aromatase inhibitors (AIs) are widely used as adjuvant treatment for estrogen-receptor
positive breast cancer in post-menopausal women. AIs have been demonstrated to have equal to
or greater efficacy and less toxicity than tamoxifen (TAM), the drug of choice for many
years. Exemestane (EXE) is a 3rd-generation AI that has demonstrated efficacy in the
treatment of breast cancer patients, and as with TAM and other AIs, there has been
considerable inter-individual variability in overall response to EXE and in the occurrence
of toxicities, but the causes of this variability have not been elucidated. Differences in
drug metabolism can be a source of variability between patients. Genetic variations occur in
several of the enzymes involved in phase I and II metabolic reactions and many of these can
lead to alterations in enzyme activity which in turn can alter therapeutic response to
drugs. EXE is extensively metabolized as unchanged EXE and is found at less than 1% in urine
and 10% in plasma. EXE pharmacokinetics will be established in a series of 20 subjects
taking EXE. EXE metabolites will then be measured at an optimal time post-EXE dose in the
urine of 200 breast cancer patients being treated with EXE to establish whether metabolizing
enzyme genotype-EXE metabolism phenotype correlations exist in vivo.

Inclusion Criteria:

- Breast cancer patients who have ER+ tumors and are taking 25 mg EXE daily (orally)

- Post-menopausal women or chemically post-menopausal women (who won't become pregnant
since they are taking zoladex), or women who are post-menopausal as a result of ovary

- Patients may be at any point in their hormonal treatment, but must have completed any
planned surgery, radiation and chemotherapy.

Exclusion Criteria:

- Concurrent use of corticosteroids, megestrol, or phenobarbitol (inhaled
and internasal steroids are permitted)

- History of allergy to exemestane

Type of Study:


Study Design:

Observational Model: Case-Only, Time Perspective: Prospective

Outcome Measure:

Metabolizing enzyme genotype vs EXE metabolism profiles

Outcome Description:

Functional genotypes will be determined for EXE-metabolizing enzymes and will be correlated with blood/urinary EXE metabolism profiles

Outcome Time Frame:

6 years

Safety Issue:


Principal Investigator

Philip Lazarus, Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Penn State College of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

September 2011

Completion Date:

January 2017

Related Keywords:

  • Breast Cancer
  • Exemestane
  • Metabolism
  • Metabolizing enzyme genotype
  • Breast cancer
  • Breast Neoplasms



Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania  17033