This randomized phase I trial studies the side effects and the best dose of letrozole in preventing breast cancer in healthy postmenopausal women at high risk for breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of letrozole may keep cancer from forming in healthy postmenopausal women at high risk for breast cancer.
PRIMARY OBJECTIVES: I. Compare the effect of lower and intermittent doses of letrozole to standard letrozole therapy on estrogen suppression in postmenopausal women at high risk for developing breast cancer. SECONDARY OBJECTIVES: I. Comparison of the effect of lower and intermittent doses of letrozole to standard therapy on signs and symptoms of estrogen deficiency, including menopausal symptoms, serum lipid profile, and serum marker of bone turnover. II. Comparison of the effect of lower and intermittent doses of letrozole to standard therapy on nuclear chromatin abnormality of breast epithelial cells collected by random periareolar fine needle aspiration (RPFNA). TERTIARY OBJECTIVES: I. Determine the prevalence of breast cancer stem cells in the fine needle breast aspirates and explore the potential intervention effect on the prevalence of breast cancer stem cells. OUTLINE: Patients are randomized to 1 of 4 treatment arms. ARM I: Patients receive 2.5 mg of letrozole orally (PO) thrice weekly for 6 months. ARM II: Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months. ARM III: Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months. ARM IV: Patients receive 2.5 mg of letrozole PO once daily for 6 months. After completion of study treatment, patients are followed up at week 30.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
112
Arizona Cancer Center - Tucson
Tucson, Arizona, United States
University of Arizona Health Sciences Center
Tucson, Arizona, United States
Mayo Clinic
Rochester, Minnesota, United States
Percentage of serum estradiol suppression in postmenopausal women at high risk for breast cancer
Three one-sided two-sample t-tests will be conducted on the ratios of the mean percentage of suppression simultaneously to test for non-inferiority. A multivariate t-distribution is used to derive the critical value and the power.
Time frame: Baseline to week 30
Change in serum estrone levels
Three one-sided two-sample t-tests will be performed to evaluate the ratio of the mean changes (or percentage of changes) of each of the three intermittent dosing groups to that of the standard therapy control group simultaneously for each of the endpoints at an overall significance level of 5%.
Time frame: Baseline to week 30
Change in serum testosterone levels
Three one-sided two-sample t-tests will be performed to evaluate the ratio of the mean changes (or percentage of changes) of each of the three intermittent dosing groups to that of the standard therapy control group simultaneously for each of the endpoints at an overall significance level of 5%.
Time frame: Baseline to week 30
Menopausal symptoms as assessed by quality of life measures, as assessed by Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Menopause Specific Quality of Life Questionnaire (MENQOL)
Time frame: Up to week 30
Nuclear chromatin abnormality as assessed by karyometry
Time frame: Up to week 30
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