NSAID Effects on Clinical and Imaging Breast Biomarkers

Study Overview
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Brief Summary
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This study has two purposes. One is to determine if daily sulindac decreases breast density; a risk factor for breast cancer development. The second is to determine whether sulindac reduces pain and stiffness associated with regular use of aromatase inhibitors given for the treatment of breast cancer.

Detailed Description
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To accomplish our study aims, we will conduct a phase II, single are trial of sulindac in postmenopausal women with early stage ER+ breast cancer who are receiving an aromatase inhibitor as adjuvant hormonal therapy. Approximately 75 breast cancer patients, stable on AI therapy (minimum of 3 months) for the treatment of their breast cancer will receive sulindac 150 mg bid for 12 months. Breast imaging will be conducted at baseline, 6 and 12 months. The primary endpoint of the study will be change in the appearance of the contralateral, uninvolved breast as measured by quantitative Fat Water Ratio (FWR-MRI) mapping at 12 months in response to sulindac therapy. As changes in breast density in the contralateral, uninvolved breast will be the primary endpoint of the study, patients with bilateral breast cancer or those patients undergoing bilateral mastectomies or reconstruction surgery will be ineligible. Secondary endpoints of the trial include 12 month change in general pain and joint specific stiffness and pain as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). A number of exploratory endpoints are planned and include comparison of MRI measures of the breast, tissue biomarkers, and pain at 6 months as early indicators of 12 month responses. For the tissue biomarkers, core needle biopsies will be obtained in a subset of women who consent to the procedure from the uninvolved contralateral breast at baseline and at 6 months. Tissue studies will include characterization of tissue histology (graded by cellularity and stromal elements) and molecular measures of proliferation and apoptosis.

Official Title
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NSAID Effects on Clinical and Imaging Breast Biomarkers

Conditions
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Inflammation, Cancer, Pain, Hypertension

Intervention / Treatment
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* Drug: Sulindac


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligibility criteria will include: Postmenopausal women with of first incidence of early stage (stages 0 - III) hormone receptor positive breast cancer stabilized on anastrozole therapy for at least 3 months Patients must have started on anastrozole and plan to continue on anastrozole therapy for a minimum of 12 months Patients must have an unaffected, non-irradiated contralateral breast with a baseline breast density score of > 25% as measured by standard digital mammography (BIRADs score > 2) or magnetic resonance imaging (MRI) performed within 12 months of randomization to the study A willingness to follow the study protocol, as indicated by provision of informed consent to participate A willingness to avoid taking NSAIDs outside of the trial (rare NSAID use for musculoskeletal symptoms excepted) Normal renal function as determined by a serum creatinine < upper limit of normal No known contraindication to NSAID use Normotensive or controlled blood pressure (< 140/90) on a single anti-hypertensive medication Exclusion Criteria: Current or anticipated need for daily aspirin or NSAID use including aspirin for cardiovascular protection Known intolerance to NSAIDs Age > 75 years History of cardiovascular disease including prior myocardial infarction, angina, stroke, or transient ischemic attack (TIA) Diabetes requiring drug therapy Current smoker History of Uncontrolled hypertension Blood pressure > 140/90 at baseline by home monitoring History of GI ulcers, chronic GERD, or GI bleeding in the past 5 years History of a bleeding diathesis or current anticoagulant therapy Daily therapy with H2 blockers or protein pump inhibitors History of claustrophobia Have electrically, magnetically, or mechanically activated implants including cardiac pacemaker, cochlear implants, magnetic surgical clips or prostheses.

Ages Eligible for Study
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Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sulindac (Clinoril)<br>Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will receive 150 mg of sulindac twice daily for 12 months. They will receive up to 4 MRI within 12 months. | Drug: Sulindac<br> <br> * Other names: Clinoril;|
| No Intervention: Observational<br>Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will continue their treatment will be monitored with MRI and standard of care tests every 6 months for up to 12 months. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Breast Density Measured as Fat to Water Ratio by Magnetic Resonance Imaging | Adjusted estimates of relative change in percent breast density by magnetic resonance imaging | Baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle and Joint Pain and Stiffness | The endpoint for arthralgia is change from baseline in Total Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index scores on a scale at 12 months. The Western Ontario and McMaster Universities Index is a self-administered questionnaire consisting of 24 items divided in 3 subscales: Pain, Stiffness, and Physical Function. Scores on the scale range from 0 to 96 for total WOMAC where 0 represents the best health status and 96 the worst possible status. | Baseline and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, breast density, chemoprevention