Effect of Aspirin on Mammogram Density in Healthy Postmenopausal Women With a Moderate or High Level of Breast Density

Study Overview
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Brief Summary
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RATIONALE: Aspirin may be effective in reducing breast density in healthy postmenopausal women with a moderate or high level of breast density. PURPOSE: This randomized clinical trial is studying the effect of aspirin on mammogram density compared with a placebo in healthy postmenopausal women with a moderate or high level of breast density.

Detailed Description
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OBJECTIVES: Primary Compare the effect of acetylsalicylic acid (aspirin) vs placebo on mammographic density in healthy postmenopausal women with a moderate or high level of breast density. Secondary Determine whether there is a differential response in mammogram density to aspirin treatments in individual homozygous wild-type, heterozygous, and homozygous variant for several UGT gene polymorphisms. Determine the effect of aspirin therapy on potential adverse events, including gastrointestinal symptoms and signs, bleeding events, blood pressure, and other major comorbidities and hospitalizations, as well as generalized symptoms, in these participants. Determine the effects of aspirin therapy on putative biomarkers of breast and ovarian cancer that are currently being validated as part of ongoing Fred Hutchinson Cancer Research Center Ovarian SPORE activities. Determine the effects of aspirin therapy on levels of serum estradiol, estrone and sex hormone binding globulin (SHBG) as measured by radioimmunoassay at baseline and 6 month timepoints OUTLINE: This is a randomized, placebo-controlled, double-blind study. Participants are randomized to 1 of 2 treatment arms. Arm I: Participants receive oral acetylsalicylic acid (aspirin) daily for 6 months. Arm II: Participants receive oral placebo daily for 6 months. In both arms, participants undergo a repeat mammogram at 6 months. Blood and urine samples are collected at baseline and at 6 months. Single-nucleotide polymorphisms in the UGT genes and variable number of tandem repeat-type polymorphisms are genotyped. PROJECTED ACCRUAL: A total of 144 participants will be accrued for this study.

Official Title
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The Effect of Aspirin on Mammogram Density (TEAM)

Conditions
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Mammographic Breast Density

Intervention / Treatment
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* Drug: Aspirin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Moderate or high density breast tissue on mammogram within the past 4 months Breast Imaging-Reporting and Data System (BIRAD) class 2-4 or digitized mammogram with ≥ 25% density Healthy without serious comorbidities Female Postmenopausal More than 3 weeks since prior and no other concurrent use (2 or more times per week) of acetylsalicylic acid (aspirin), ibuprofen, or other NSAIDs EXCLUSION CRITERIA: history of breast cancer, including ductal carcinoma in situ or lobular carcinoma in situ history of illness for which NSAIDs are typically primary therapy (e.g., rheumatoid arthritis) Allergy to NSAIDs Anemia (hematocrit < 35%), abnormal bleeding tests, or bleeding disorders Gastrointestinal (GI) ulcer or history of GI bleeding Adverse reactions to aspirin acid or other NSAIDs Renal disease Asthma Current or chronic liver disease History of hemorrhagic stroke or transient ischemic attack History of coronary artery disease, including any of the following: Myocardial infarction (MI) Angina Coronary artery disease documented on cardiac catheterization, exercise thallium, or exercise echocardiogram Strong family history of coronary artery disease (i.e., mother with MI before 55 years of age, father with MI before 45 years of age) Documented carotid artery disease Diabetes Uncontrolled hypertension No planned extensive weight loss in the next 6 months (≥ 10 pounds) More than 2 alcoholic drinks daily Mental illness or alcohol or drug abuse Prior angioplasty or coronary artery bypass grafting Prior breast implantation or reduction surgery Less than 6 months since prior hormones for menopause (including pills, patches, vaginal route), tamoxifen citrate, raloxifene, other hormonal therapy, or herbal or soy preparations Concurrent anticoagulation medication

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aspirin<br> | Drug: Aspirin<br>* Two 325 mg doses of aspirin per day for 6 months<br>* Other names: Acetylsalicylic acid;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Two placebo pills per day for 6 months<br>* Other names: Placebo, sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the effect of acetylsalicylic acid (aspirin) vs placebo on mammographic density |  | Baseline and end-of-study (6 month timepoint) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differential response in mammogram density to aspirin treatments in individual homozygous wild-type, heterozygous, and homozygous variant for several UGT gene polymorphisms | Changes at baseline and 6 month timepoint in mammographic density; measurements of single numcleotide polymorphisms in specific genes from a single DNA samples | Baseline and end-of-study (6 month timepoint) | 
| Adverse events |  | Collected over the course of tehestudy | 
| Putative biomarkers of breast and ovarian cancer |  | Baseline and end-of-study (6 month timepoint) | 
| Comparison of the effect of aspiring vs placebo on serum levels of estradiol, estrone and sex hormone binding globulin |  | Baseline and 6 month timepoints | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mammographic breast density aspirin