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Understanding the role of adiposity and adipokine-related RNA expression in the tumor microenvironment on breast cancer outcomes in a racially and ethnically diverse sample

Award Number: R01CA277862
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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Understanding the role of adiposity and adipokine-related RNA expression in the tumor microenvironment on breast cancer outcomes in a racially and ethnically diverse sample - The mechanisms linking adiposity with breast cancer and how variation in adipose tissue distribution contributes to breast cancer recurrence and mortality remain to be determined. Untangling the complex interactions among adiposity and breast tumor phenotype is a first step, which requires precise adiposity measures and identification and refinement of adiposity-associated biomarkers within breast tumor tissues that can predict breast cancer outcomes. Our preliminary research has shown that the distribution of visceral adipose tissue and subcutaneous adipose tissue – assessed by computed tomography (CT) – scans differ by sociodemographic factors and outperforms body mass index (BMI) in predicting cancer outcomes. Our prior research also shows that gene and protein expression of the adipokines, leptin and adiponectin, and their receptors vary in breast tumor tissues and generally, lower expression is associated with more aggressive tumor features (e.g., higher grade, larger size, hormone receptor negative status, and triple-negative subtype). Further, increased body fatness measures – general obesity (BMI), body fat distribution (waist circumference, hip circumference, WHR), and body composition (fat mass index, percent body fat) – are associated with higher leptin receptor protein expression in breast tumor tissues, with evidence of effect modification by sociodemographics. Building on these preliminary studies, we hypothesize that adipose tissue depots (visceral vs. subcutaneous) have differing associations with adipokine and adipokine receptor expression profiles and related gene signatures in the breast tumor microenvironment (TME). Using multiplex RNA in situ hybridization to characterize the abundance of adipokine and adipokine receptor expression in the breast TME, CT scans to assess adipose tissue distribution, and RNA-seq for transcriptomic analysis in a large cohort of 1600 women with breast cancer, we will: (1) Test whether adiposity is associated with cell type-specific RNA expression profiles of leptin, adiponectin, and their receptors in breast tumors and the adjacent breast TME; (2) Define associations between RNA expression profiles of leptin, adiponectin, and their receptors in the breast TME with tumor clinicopathology; and (3) Characterize RNA expression profiles associated with leptin, adiponectin, and their receptors in the breast TME to predict breast cancer recurrence and mortality. This study will yield novel insights on how adipose tissue distribution impacts gene expression profiles in the breast TME and new information about potential differences by tumor subtype. Such data are critical for efforts to integrate tumor markers and systemic factors into breast cancer risk and outcome prediction models, and to informing the development of precision prevention interventions and precision therapeutics for breast cancer patients.


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 = $704,598 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Cause and Prevention Research	000	3	1/29/2026	NON-COMPETING CONTINUATION	$634,138
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Cause and Prevention Research	001	3	4/16/2026	NON-COMPETING CONTINUATION	$70,460
														Subtotal = $704,598

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Cause and Prevention Research	000	2	3/20/2025	NON-COMPETING CONTINUATION	$0
2025	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Cause and Prevention Research	001	2	3/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $671,015 )
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Cause and Prevention Research	000	2	11/30/2023	NON-COMPETING CONTINUATION	$635,699
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Cause and Prevention Research	001	2	4/17/2024	NON-COMPETING CONTINUATION	$35,316
														Subtotal = $671,015

Issue Date FY: 2023 ( Subtotal = $735,278 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Cause and Prevention Research	000	1	12/1/2022	NEW	$735,278
														Subtotal = $735,278

Grand Total All Awards = $2,110,891

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Understanding the role of adiposity and adipokine-related RNA expression in the tumor microenvironment on breast cancer outcomes in a racially and ethnically diverse sample

Award Number: R01CA277862

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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