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Involution-based biomarkers of breast cancer risk

Award Number: R01CA237602
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Involution-based biomarkers of breast cancer risk - PROJECT SUMMARY/ABSTRACT The breast lobules are the structures that produce milk in lactating women, and are also the primary site of origin for breast cancer. Age-related lobular involution (LI) is a physiological process in which the epithelial tissue of the breast lobules gradually regresses with age, corresponding with elimination of the need for milk production beyond the child-bearing years. Analysis of our cohort of more than 14,000 women with benign breast disease (BBD) revealed that LI is strongly associated with reduced risk of subsequent breast cancer, and thus LI constitutes a natural mechanism for prevention of breast cancer. However, more than 40% of postmenopausal women with BBD have not completed LI, and these women are at substantially greater risk of developing breast cancer compared to women of similar age whose involution process has completed. In this application, we propose experiments to identify critical effectors of LI and to determine how these can be used to improve breast cancer risk assessment for women who have not undergone LI. In Aim 1, we will define the mediators that underlie the link between delayed LI and a high risk cellular phenotype. We will use a newly- generated panel of very early passage primary human mammary epithelial cells (HMECs) derived from women with BBD and varying degrees of LI, in combination with humanized mouse xenograft models in which the LI status of the HMECs is manifest. In Aim 2, we will identify mediators associated with ongoing vs delayed LI in a newly-defined clinical cohort of peri- and post-menopausal women for whom multiple, sequential benign biopsies are available. In Aim 3, biomarkers discovered in Aims 1 and 2 (plus other promising biomarkers) will be evaluated for association with subsequent breast cancer in a patient cohort of postmenopausal women. The cohorts interrogated in Aims 2 and 3 will be drawn both from the Mayo Clinic BBD cohort, which is primarily composed of White/Caucasian women, and the Detroit BBD cohort, which is composed of Black/African-American women, which will allow us to evaluate race as a biological variable in our analyses. By providing insight into the processes that control LI and by developing tractable experimental models in which to evaluate the effects of modulating those processes, our work will provide a better understanding of LI delay and its link to breast cancer and will point toward methods for inducing LI in women for whom this process is stalled or delayed, as a physiologically-derived method for breast cancer prevention.


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 = -$36,497 )
2026	2024	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Detection and Diagnosis Research	000	5	11/21/2025	NON-COMPETING CONTINUATION	-$36,497
														Subtotal = -$36,497

Issue Date FY: 2024 ( Subtotal = $614,934 )
2024	2024	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Detection and Diagnosis Research	001	5	5/2/2024	SUPPLEMENT FOR EXPANSION	$141,218
2024	2024	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Detection and Diagnosis Research	000	5	5/1/2024	NON-COMPETING CONTINUATION	$473,716
														Subtotal = $614,934

Issue Date FY: 2023 ( Subtotal = $635,213 )
2023	2023	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Detection and Diagnosis Research	000	4	6/9/2023	NON-COMPETING CONTINUATION	$486,563
2023	2023	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Detection and Diagnosis Research	001	4	6/13/2023	SUPPLEMENT FOR EXPANSION	$148,650
														Subtotal = $635,213

Issue Date FY: 2022 ( Subtotal = $488,556 )
2022	2022	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Detection and Diagnosis Research	000	3	5/25/2022	NON-COMPETING CONTINUATION	$488,556
														Subtotal = $488,556

Issue Date FY: 2021 ( Subtotal = $507,487 )
2021	2021	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Detection and Diagnosis Research	000	2	5/17/2021	NON-COMPETING CONTINUATION	$507,487
														Subtotal = $507,487

Issue Date FY: 2020 ( Subtotal = $554,827 )
2020	2020	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Detection and Diagnosis Research	000	1	8/24/2020	NEW	$554,827
														Subtotal = $554,827

Grand Total All Awards = $2,764,520

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Involution-based biomarkers of breast cancer risk

Award Number: R01CA237602

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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