Clinical trial NCT00470561: Effect of Aspirin on Mammogram Density in Healthy Postmenopausal Women With a Moderate or High Level of Breast Density
Official title: The Effect of Aspirin on Mammogram Density (TEAM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mammographic Breast Density
Keywords: mammographic breast density aspirin
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-05-07
Enrollment: 144
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Comparison of the effect of acetylsalicylic acid (aspirin) vs placebo on mammographic density
timeFrame: Baseline and end-of-study (6 month timepoint)
Secondary outcomes:
measure: Differential response in mammogram density to aspirin treatments in individual homozygous wild-type, heterozygous, and homozygous variant for several UGT gene polymorphisms
timeFrame: Baseline and end-of-study (6 month timepoint)
measure: Adverse events
timeFrame: Collected over the course of tehestudy
measure: Putative biomarkers of breast and ovarian cancer
timeFrame: Baseline and end-of-study (6 month timepoint)
measure: Comparison of the effect of aspiring vs placebo on serum levels of estradiol, estrone and sex hormone binding globulin
timeFrame: Baseline and 6 month timepoints
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Nicole Urban, ScD
role: STUDY_CHAIR
References: