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Breast White Adipose Tissue Inflammation and Breast Cancer Outcomes

Award Number: R01CA241409
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Breast White Adipose Tissue Inflammation and Breast Cancer Outcomes - ABSTRACT Obesity and excess adiposity at the time of breast cancer diagnosis are associated with increased likelihood of recurrence and cancer-related death. Understanding the mechanisms by which excess adiposity affects breast cancer progression would provide critical insights into strategies to improve patient outcomes. We have identified a novel tissue-based inflammatory biomarker in breast adipose tissue, crown-like structures of the breast (CLS-B), that we have shown to be associated with obesity and dysregulated metabolic factors. The presence of CLS-B, which are comprised of an adipocyte surrounded by a “crown” of macrophages, indicates a state of inflammation in the breast white adipose tissue (B-WATi). We previously reported that B- WATi is associated with metabolic syndrome characteristics. Importantly, B-WATi is associated with increased breast cancer risk and shortened time to recurrence in women with metastatic disease. The Pathways Study, a prospective cohort study of women with invasive breast cancer supported by an NCI cancer epidemiology cohort infrastructure grant, provides an outstanding opportunity to conduct a large- scale, definitive investigation of the pathophysiologic state associated with B-WATi, and to investigate the association of B-WATi with breast cancer outcomes. From January 2006 to May 2013, we enrolled a racially- and ethnically-diverse cohort of 4,505 women soon after a breast cancer diagnosis in Kaiser Permanente Northern California (KPNC). Pathways Study participants provided blood specimens and reported on lifestyle factors, including diet and physical activity. Linkage to KPNC electronic health records captures details of cancer diagnosis and clinical care, and a biorepository of diagnostic slides and formalin-fixed, paraffin- embedded tissue blocks has been created from definitive breast cancer surgeries for all cohort members. We propose to determine B-WATi presence and severity in Pathways Study participants who underwent mastectomy (n=1,982), leveraging the substantial non-tumor breast tissue available in the biorepository. We also propose to assay systemic measures of inflammation and metabolic aberration, and examine measures of adipose tissue distribution in a subset of women with computed tomography (CT) images. Specific Aims are to: 1) Characterize the pathophysiological state of B-WATi in women with invasive breast cancer, including associations with lifestyle factors, adipose tissue distribution, and circulating cytokine and metabolic profiles; 2) Determine the associations between B-WATi and breast cancer outcomes; and, 3) Examine whether the associations between B-WATi and breast cancer outcomes vary by lifestyle factors and other breast cancer prognostic factors such as race/ethnicity, hormone receptor status, stage of disease, and breast cancer treatment. This project brings together ground-breaking and innovative work on B-WATi with the outstanding resources and infrastructure of the Pathways Study. It promises to provide insight into the impact of B-WATi on breast cancer and to identify actionable and modifiable risk factors to improve breast cancer outcomes.


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 = $710,316 )
2024	2024	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	000	5	4/12/2024	NON-COMPETING CONTINUATION	$710,316
														Subtotal = $710,316

Issue Date FY: 2023 ( Subtotal = $920,624 )
2023	2023	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	000	4	5/5/2023	NON-COMPETING CONTINUATION	$920,624
														Subtotal = $920,624

Issue Date FY: 2022 ( Subtotal = $926,607 )
2022	2022	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	000	3	5/25/2022	NON-COMPETING CONTINUATION	$926,607
														Subtotal = $926,607

Issue Date FY: 2021 ( Subtotal = $972,130 )
2021	2021	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	000	2	4/26/2021	NON-COMPETING CONTINUATION	$972,130
														Subtotal = $972,130

Issue Date FY: 2020 ( Subtotal = $981,204 )
2020	2020	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	000	1	4/24/2020	NEW	$981,204
														Subtotal = $981,204

Grand Total All Awards = $4,510,881

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Breast White Adipose Tissue Inflammation and Breast Cancer Outcomes

Award Number: R01CA241409

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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