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

Award Number: R01CA235720
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $597,059 )
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	000	5	2/8/2024	NON-COMPETING CONTINUATION	$565,633
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	001	5	4/17/2024	NON-COMPETING CONTINUATION	$31,426
														Subtotal = $597,059

Issue Date FY: 2023 ( Subtotal = $702,967 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	000	4	3/31/2023	NON-COMPETING CONTINUATION	$702,967
														Subtotal = $702,967

Issue Date FY: 2022 ( Subtotal = $567,232 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	001	3	5/3/2022	NON-COMPETING CONTINUATION	$46,306
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	000	3	3/1/2022	NON-COMPETING CONTINUATION	$520,926
														Subtotal = $567,232

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	000	2	8/20/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $581,171 )
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	001	2	9/14/2020	NON-COMPETING CONTINUATION	$581,171
2020	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	000	1	8/31/2020	NEW	$0
														Subtotal = $581,171

Issue Date FY: 2019 ( Subtotal = $546,274 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	000	1	9/20/2019	NEW	$546,274
														Subtotal = $546,274

Grand Total All Awards = $2,994,703

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

Award Number: R01CA235720

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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