# Three-Arm randomized trial comparing the effect of aspirin, sulindac or no treatment control on breast density in patients with elevated breast cancer risk

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $597,059

## Abstract

Project Abstract
Despite advances in early detection and treatment, breast cancer remains a major cause of
morbidity and mortality in women and prevention a major unmet need. Non-steroidal anti-
inflammatory agents (NSAIDs), including aspirin (ASA), are among the most widely used drugs
for minor pain and arthritis that demonstrate anti-tumor activity. Based on epidemiological data,
low dose ASA is under investigation in clinical trials for the prevention of breast cancer
recurrence. We were previously funded to perform a clinical trial of the NSAID, sulindac (SUL)
at 150 mg BID, in postmenopausal women receiving aromatase inhibitor therapy as part of their
breast cancer care. In an interim analysis, SUL significantly reduced breast density determined
by MRI compared to an observation, control group after 12 months. Further, SUL reduced
collagen straightness in breast tissue by second harmonic generation microscopy (SHG)
microscopy and the change was significantly correlated with a decrease in breast density.
Additional MRI based imaging of breast adipose tissue suggest novel SUL effects consistent
with effects on anti-inflammatory/anti-tumor M2 type macrophages in adipose. SUL is a unique
pro-drug with cyclooxygenase (COX) and non-COX activities. Because of unique anti-cancer
activity in preclinical models and clinical trials, SUL has been studied for more than two decades
and recently granted Fast Track Status by the FDA in combination with CPP-1X for approval as
a chemoprevention agent for patients with familial adenomatous polyposis. Activity of SUL in
preclinical models to prevent epithelial cancers support similar anti-cancer action in the breast.
Our new data extend the preclinical findings to effects on breast density; an established risk
factor for breast cancer. Here we propose to follow our promising preliminary data with the
natural next step of a randomized, open label 3 arm study of SUL 150 mg BID, ASA 325 mg QD
and no treatment control in postmenopausal women at increased risk of developing breast
cancer. We will test the hypothesis that SUL at 150 mg BID for 12 months will significantly
lower breast density in at-risk women and be superior to ASA, a cheaper, more accessible, and
perhaps safer NSAID. Secondarily, paired breast biopsies (baseline and after 6 months) will be
used to test the hypothesis that SUL effects on breast density are partly mediated through
effects on breast tissue collagen alignment and collagen expression using highly innovative
SHG and whole tissue slide matrix assisted laser desorption ionization (MALDI)-mass
spectrometry. In addition, we will explore SUL and ASA effects on breast adipose including
novel hypotheses that their action is in part mediated through activity on macrophages in breast
tissue.

## Key facts

- **NIH application ID:** 10819207
- **Project number:** 5R01CA235720-05
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Alison T. STOPECK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $597,059
- **Award type:** 5
- **Project period:** 2019-09-20 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819207

## Citation

> US National Institutes of Health, RePORTER application 10819207, Three-Arm randomized trial comparing the effect of aspirin, sulindac or no treatment control on breast density in patients with elevated breast cancer risk (5R01CA235720-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10819207. Licensed CC0.

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