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Menopausal transition - a window of susceptibility for the promotion of breast cancer by environmental exposures

Award Number: U01ES026137
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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¿ DESCRIPTION (provided by applicant):There is substantial evidence suggesting that environmental disrupting chemicals (EDCs) initiate and promote the development of breast cancer. In this U01 application, we will study an under-investigated window of susceptibility for exposure: the menopausal transition. This transition begins when ovarian function begins to decline and ends at menopause when there is a cessation of ovarian function resulting in low levels of estrogens. During this important window of susceptibility, the Women's' Health Initiative (WHI) reported that hormone therapy increased both the incidence of and mortality from breast cancer. The WHI results are explained by a biologically-based breast tumor model; it suggests that hormone therapy in the menopausal transition promotes the growth of pre-existing occult lesions and minimally initiated de novo tumors. We hypothesize that EDCs mimic hormone therapy and promote the development of breast cancer during the menopausal transition. We will focus on polybrominated diphenyl ethers (PBDEs) because of their persistence in the environment and human tissue and on bisphenol A (BPA) because of its widespread use in food-grade plastics and thermal paper. Both EDCs are recognized as major health concerns. Our proposed research will allow us to evaluate the role of these EDCs, individually and combined, on the development of breast cancer during the menopausal transition. To determine the mechanisms, we will apply a transdisciplinary approach using cell culture, samples collected from women during the menopausal transition, and mouse models. In Specific Aim 1, we will determine the biologic actions and mechanisms of EDCs, singly and in combination, using the AroER-Tri screen cell culture system developed by the joint-Principal Investigator, Dr. Chen. In Specific Aim 2, we will assess the effects of EDCs in women during the menopausal transition on estrogenic activity and the epigenome, as well as the association of the EDCs and breast cancer. In Specific Aim 3, we will test the effects of these EDCs on the development of mammary lesions in a mouse model of menopause, and compare to the effects in an ovarectomized mouse model. Our transdisciplinary approach will capitalize on the strengths of each study type and allow us to conduct a more comprehensive assessment than any single approach. This is possible because of our experienced, multidisciplinary team. In Specific Aim 4, with our community partners, we will provide a one-stop web-based resource for evidence-based materials on the role of environmental exposures and development of breast cancer, particularly during the menopausal transition. Furthermore, we will develop, test, and disseminate educational materials to multi-culturally diverse communities. We will share our expertise/work with other multi-disciplinary teams in the BCERP to produce valuable results and increase the amount of relevant scientific knowledge on the mechanisms and effects of EDC exposure. We expect this work to result in future prevention strategies to reduce or mitigate exposures and promote effective communication of scientifically sound findings to the general public and policy makers.


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: 2023 ( Subtotal = $2 )
2023	2019	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	000	5	11/23/2022	NON-COMPETING CONTINUATION	$2
														Subtotal = $2

Issue Date FY: 2022 ( Subtotal = -$2 )
2022	2019	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	000	5	2/22/2022	NON-COMPETING CONTINUATION	-$2
														Subtotal = -$2

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	000	5	12/17/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $891,750 )
2019	2019	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	001	5	6/14/2019	NON-COMPETING CONTINUATION	$891,750
2019	2018	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	000	4	12/21/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $891,750

Issue Date FY: 2018 ( Subtotal = $945,498 )
2018	2018	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	002	4	6/25/2018	NON-COMPETING CONTINUATION	$945,498
2018	2017	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	001	3	12/22/2017	NON-COMPETING CONTINUATION	$0
2018	2017	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	000	3	12/21/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $945,498

Issue Date FY: 2017 ( Subtotal = $977,907 )
2017	2017	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	000	3	6/30/2017	NON-COMPETING CONTINUATION	$977,907
														Subtotal = $977,907

Issue Date FY: 2016 ( Subtotal = $989,046 )
2016	2016	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1450 EAST DUARTE ROAD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	000	2	6/30/2016	NON-COMPETING CONTINUATION	$989,046
														Subtotal = $989,046

Issue Date FY: 2015 ( Subtotal = $1,018,271 )
2015	2015	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1450 EAST DUARTE ROAD	DUARTE	CA	91010	LOS ANGELES	USA	Environmental Health	000	1	9/24/2015	NEW	$1,018,271
														Subtotal = $1,018,271

Grand Total All Awards = $4,822,472

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Menopausal transition - a window of susceptibility for the promotion of breast cancer by environmental exposures

Award Number: U01ES026137

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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