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Taking AIM at Breast Cancer: Targeting Adiposity and Inflammation with Movement to Improve Prognosis in Breast Cancer Survivors

Award Number: R01CA214385
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Taking AIM at Breast Cancer: Targeting Adiposity and Inflammation with Movement to Improve Prognosis in Breast Cancer Survivors - Targeting chronic inflammation related to obesity with exercise has the potential to improve prognosis in obese postmenopausal breast cancer survivors. Obesity is considered a leading modifiable contributor to breast cancer mortality worldwide due to its association with increased recurrence and decreased overall survival rate. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in adipose tissue. In particular, white adipose tissue (WAT) is a metabolically complex organ comprised of adipocytes capable of secreting adipokines and proinflammatory cytokines related to tumorigenesis. Chronic inflammation of WAT includes accumulation of adipose tissue macrophages (ATMs). Specifically, the ATM M1 phenotype, elevated with obesity, provides a rich source of cytokines, which are key mediators of obesity-associated insulin resistance. Gains in fat mass and a decline in lean mass, known as sarcopenic obesity, are observed as a treatment side effect, further contributing to the development of WAT and subsequent elevated M1 expression. Favorably, exercise-induced changes in sarcopenic obesity lead to a reduction in M1 ATMs, and increase in M2 ATMs known to protect against insulin resistance by attenuating inflammation. However it is unknown what impact this may have on cancer prognosis and what forms of exercise are most effective at reducing chronic inflammation. Our general hypothesis is that exercise designed to target chronic inflammation and associated sarcopenic obesity will improve prognosis in obese postmenopausal breast cancer survivors. We propose a Phase II RCT to compare the effects of two combined aerobic and resistance exercise interventions relative to an attention control group among early-stage obese postmenopausal breast cancer survivors who have completed primary cancer therapy. This proposal will address the following aims: 1) determine the effects of exercise on obesity-associated chronic inflammation; 2) examine the effects of exercise on sarcopenic obesity; 3) determine the effects of exercise on breast cancer prognosis and to assess whether reductions in chronic inflammation are associated with breast cancer prognosis. This study is innovative because a) we will target adipose tissue inflammatory biomarkers to improve cancer prognosis, b) derive a mathematical model that employs measureable markers of inflammation to predict prognosis, c) utilize a novel biopsy method to obtain deep subcutaneous abdominal adipose tissue to address a mechanistic prognostic question, and d) employ a unique periodized, circuit-style exercise design to reduce chronic inflammation. If the aims are achieved, findings from this study will generate new knowledge about exercise guidelines for breast cancer survivors most likely to improve prognosis. !


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: 2026 ( Subtotal = -$2,087 )
2026	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	6	12/18/2025	NON-COMPETING CONTINUATION	-$2,087
														Subtotal = -$2,087

Issue Date FY: 2023 ( Subtotal = $610,690 )
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	6	8/16/2023	NON-COMPETING CONTINUATION	$610,690
														Subtotal = $610,690

Issue Date FY: 2022 ( Subtotal = $623,101 )
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	5	8/18/2022	NON-COMPETING CONTINUATION	$623,101
2022	2018	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	001	2	9/26/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $623,101

Issue Date FY: 2021 ( Subtotal = $611,422 )
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	002	4	8/26/2021	NON-COMPETING CONTINUATION	$611,422
2021	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	3	11/2/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$469,695
2021	2018	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	2	11/2/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$469,695
														Subtotal = $611,422

Issue Date FY: 2020 ( Subtotal = $597,065 )
2020	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	003	3	9/4/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2020	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	002	3	8/31/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$597,065
2020	2018	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	001	2	8/31/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2020	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	1	12/3/2019	NEW	$0
														Subtotal = $597,065

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	1	9/13/2019	NEW	-$561,174
2019	2018	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	001	2	9/13/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$561,174
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $636,684 )
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	1	8/15/2018	NEW	$636,684
														Subtotal = $636,684

Grand Total All Awards = $3,076,875

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Taking AIM at Breast Cancer: Targeting Adiposity and Inflammation with Movement to Improve Prognosis in Breast Cancer Survivors

Award Number: R01CA214385

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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