Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Heart and Blood Diseases

Inflammation

Breast Neoplasms

Hypertension

Pain

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antirheumatic Agents

Analgesics

Aromatase Inhibitors

Sulindac

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

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.

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.

Patricia Thompson-Carino, PhD

Alison Stopeck, MD

Pavani Chalasani, MD

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.

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.

NSAID Effects on Clinical and Imaging Breast Biomarkers

Adjusted estimate of change in mean arterial blood pressure in each study arm at 12 months in each study arm.

Adjusted estimates of relative change in percent breast density by magnetic resonance imaging

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.

Stony Brook University

Professor

Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.

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 and two breast biopsies.

Sulindac (Clinoril)

Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will continue their treatment and will be monitored with MRI and standard of care every 6 months for up to 12 months.

Observational

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.

Sulindac

Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will continue their treatment and will be monitored with MRI and standard of care tests at 6 and 12 months.

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

United States

Region of Enrollment

For baseline analyses for the sulindac arm, we included only those participants who remained in the study after the NSAID washout and who started the intervention with sulindac (n=50). For the baseline analyses for the observation arm, we included those participants who either completed their baseline MRI and/or questionnaires for the secondary arthralgia endpoints (n=50).

Dr. Alison T Stopeck

The study was designed to assess change in breast density using fat/water MRI after 12 months of sulindac intervention in postmenopausal breast cancer patients taking aromatase inhibitors for the treatment of estrogen receptor positive breast cancer. A non-randomized observation arm was included with the same eligibility criteria to assess change in breast density over 12 months using the fat/water MRI method of quantifying breast density. Change was examined separately for each arm.

Breast density data were unavailable for 4 participants in the observation group due to MRI intolerance. This reduced the sample size for the outcome of change in breast density for the observation arm compared to the secondary endpoints.

Change in Breast Density Measured as Fat to Water Ratio by Magnetic Resonance Imaging

Questionnaires for patient reported outcomes were completed at baseline for 50 participants in both sulindac and the observation group.

Muscle and Joint Pain and Stiffness

Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will receive 150 mg of sulindac twice daily for 12 months.

Blood pressure was available at baseline for 50 participants in both the sulindac and observation group.

Change in Mean Arterial Blood Pressure at 12 Months

Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will continue their standard of care treatment and be monitored with MRI for change in breast density every 6 and 12 months.

Spots Global Cancer Trial Database for breast cancer, breast density, chemoprevention