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Role of FSH in postmenopausal obesity and breast cancer

Award Number: R01CA258436
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Role of FSH in postmenopausal obesity and breast cancer - ABSTRACT There is strong and consistent evidence for an association between obesity and post-menopausal breast cancer; however, the exact mechanisms are not clear. Follicle stimulating hormone (FSH) increases with menopause, concomitant with increased adiposity, particularly visceral adipose tissue (VAT). Recent preclinical data suggests that FSH may drive the deleterious shift in adiposity, independent of estrogen (E2). Further, FSH receptors are now known to be expressed in breast tumors. To date, there have been no large- scale human investigations of these FSH-adiposity-breast cancer associations. Using the Women's Health Initiative (WHI), a long-term national epidemiologic study of postmenopausal women, we will test the hypothesis that FSH drives adiposity postmenopausally, both cross-sectionally and longitudinally. Large subsets of WHI participants completed repeat dual energy x-ray absorptiometry (DXA) scans, and therefore have available robust measures of adiposity (including a novel measure of VAT) and banked serum from the randomized hormone therapy trials (N=1400) and the observational study (OS; N=1499). Second, using a case-control design, we will test the hypothesis that higher baseline FSH levels associate with increased risk of breast cancer using adjudicated cancer incidence data spanning >25 years follow-up (N=785 cases; N=2510 non-cases). Further, we will determine whether adiposity mediates the FSH-breast cancer risk associations. For all analyses, we will account for exogenous HT use (conjugated equine estrogen ± medroxyprogesterone acetate or reported HT use in the OS), endogenous estrogen (E2), and adipose-derived hormones that directly or indirectly regulate FSH (e.g. leptin). Our study is the first comprehensive epidemiologic investigation of FSH and obesity to measure and study FSH levels in the years prior to breast cancer diagnosis to assess the potential role of FSH in breast cancer. This study, which includes rich hormone and body composition data will enable immediate translation to more precise breast cancer prevention interventions aligned with new medications in the pipeline or currently in use for other cancers and osteoporosis, such as FSH and FSH receptor modulators, upstream GnRH antagonists (e.g. goserelin), and estetrol (E4).


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: 2025 ( Subtotal = $743,147 )
2025	2025	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Cause and Prevention Research	001	4	6/2/2025	NON-COMPETING CONTINUATION	$74,315
2025	2025	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Cause and Prevention Research	000	4	1/10/2025	NON-COMPETING CONTINUATION	$668,832
														Subtotal = $743,147

Issue Date FY: 2024 ( Subtotal = $711,888 )
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Cause and Prevention Research	000	3	2/9/2024	NON-COMPETING CONTINUATION	$674,421
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Cause and Prevention Research	001	3	4/18/2024	NON-COMPETING CONTINUATION	$37,467
														Subtotal = $711,888

Issue Date FY: 2023 ( Subtotal = $738,004 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Cause and Prevention Research	000	2	3/14/2023	NON-COMPETING CONTINUATION	$738,004
														Subtotal = $738,004

Issue Date FY: 2022 ( Subtotal = $807,294 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Cause and Prevention Research	000	1	2/25/2022	NEW	$807,294
														Subtotal = $807,294

Grand Total All Awards = $3,000,333

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Role of FSH in postmenopausal obesity and breast cancer

Award Number: R01CA258436

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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