Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen citrate may fight breast cancer by blocking the use of estrogen by the tumor cells This phase IIb trial studies how well low-dose tamoxifen citrate works in reducing breast cancer risk in radiation-induced cancer survivors.
PRIMARY OBJECTIVES: I. To determine the impact of a two-year course of low-dose tamoxifen (tamoxifen citrate) administered at 5 mg per day on surrogate endpoint biomarkers of breast cancer (BC) risk, including: mammographic breast density (MBD), an established radiographic biomarker of BC risk; cytomorphology and proliferative index, tissue biomarkers closely linked to BC risk; and sex steroid hormones and insulin growth factors, circulating biomarkers of BC risk. II. To establish safety and tolerability of this low-dose tamoxifen regimen, assessing both objective measures (lipid profiles, clotting factors and bone metabolism markers) and patient-reported outcomes. III. To examine the modifying effect of demographic, clinical, and molecular characteristics on the risk: benefit ratio from this two-year low dose tamoxifen intervention. IV. To explore the relationship between this low-dose tamoxifen regimen and clinical measures of efficacy (new breast cancer and ductal carcinoma in situ \[DCIS\] diagnoses) and toxicity (thromboembolic events, reports of hot flashes and gynecological symptoms, liver function abnormalities, and other cancer diagnoses). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive tamoxifen citrate orally (PO) once daily for 24 months in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO once daily for 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 10 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
84
University of Alabama at Birmingham
Birmingham, Alabama, United States
City of Hope Medical Center
Duarte, California, United States
University of Colorado, Anschutz Medical Campus
Aurora, Colorado, United States
Mammographic Breast Density
Mammographic density was quantified as percentage of fibroglandular tissue. Using an intention-to-treat analysis, mammographic breast density (MBD) was compared between patients in the low dose tamoxifen intervention and placebo group by applying the linear mixed effects model for normally distributed data.
Time frame: At year two post treatment
Insulin Growth Factor Levels (IGF1)
IGF1 will be treated as a continuous measure. The linear mixed effects model for between group comparisons of measures from 3 time points will be applied. The unstructured mean model and linear in time model will be employed.
Time frame: Up to 2 years
Number of Grade 2-4 Toxicities
Will be tabulated by treatment arm. Differences by treatment arm will be evaluated using Fisher exact tests.
Time frame: Up to 2 years
Biomarker Levels
Total cholesterol, low and high density lipoprotein, triglycerides, and anti-thrombin III enzymatic assay measurements will be treated as continuous variables. Transformed to normality as appropriate, the linear mixed effects model will be applied, using the unstructured mean model and linear in time model to assess the effects of low-dose tamoxifen on these measurements over time.
Time frame: Up to 2 years
Percentage of Pills Taken Out of the Total Prescribed
The number of pills taken out of the total prescribed in a 3-month period will be modeled as a random effects binomial regression model. The binomial rates from 8 time points (month 3-24) will be modeled as unstructured mean model with 7 indicator variables as well as polynomial models over time. The random-intercept and the random intercept and slope models will be considered. The significance of the time indicators or parameters by treatment interaction will be evaluated for treatment difference in compliance.
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University of Chicago
Chicago, Illinois, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
Wake Forest University
Winston-Salem, North Carolina, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
...and 3 more locations
Time frame: Up to 2 years
Number of Participants With Different Patient Reported Symptoms, Measured by Questionnaire
The outcomes will be scored as a 5-point Likert-type scale (0-4) in response to questions on how much the patients are bothered by certain symptoms. The questionnaire will be administered every 6 months. The responses will be treated as normally distributed, as ordinal or dichotomized variable, and the linear mixed effects of general linear mixed model (GLMM) methods will be applied to compare changes between treatment groups. Piecewise models will also be fitted with join point at 6 months, considering linear and curvilinear trajectories between 6 and 24 month time points.
Time frame: Up to 2 years
Insulin Growth Factor Levels (IGF3 )
IGF3 will be treated as a continuous measure. The linear mixed effects model for between group comparisons of measures from 3 time points will be applied. The unstructured mean model and linear in time model will be employed.
Time frame: Up to 2 years
Biomarker Levels - Alkaline Phosphatase
Serum bone-specific alkaline phosphatase measurements will be treated as continuous variables. Transformed to normality as appropriate, the linear mixed effects model will be applied, using the unstructured mean model and linear in time model to assess the effects of low-dose tamoxifen on these measurements over time.
Time frame: Up to 2 years
Biomarker Levels - Urine N-telopeptide
Urine n-telopeptide measurements will be treated as continuous variables. Transformed to normality as appropriate, the linear mixed effects model will be applied, using the unstructured mean model and linear in time model to assess the effects of low-dose tamoxifen on these measurements over time.
Time frame: Up to 2 years