R01CA258436

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). Furthermore, 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 of follow-up (N=785 cases; N=2510 non-cases). Furthermore, we will determine whether adiposity mediates the FSH-breast cancer risk associations. For all analyses, we will account for exogenous hormone therapy use (conjugated equine estrogen ± medroxyprogesterone acetate or reported hormone therapy 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).

University Of Arizona

TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS, (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION, (3) EPIDEMIOLOGY, (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS, (5) IMMUNOLOGY AND VACCINES, (6) FIELD STUDIES AND STATISTICS, (7) CANCER CHEMOPREVENTION AND INTERCEPTION, (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT, (9) ORGAN SITE STUDIES AND CLINICAL TRIALS, (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES, AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO STIMULATE TECHNICAL INNOVATION, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

Arizona United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 272% from $807,294 to $3,000,333.