Grant Number:	1R01CA131333-01A1 Interpret this number
Primary Investigator:	Schmitz, Kathryn
Organization:	University Of Pennsylvania
Project Title:	Wiser Sister
Fiscal Year:	2008

DESCRIPTION (provided by investigator): A subset of premenopausal women is at significantly elevated risk for breast cancer due to specific genetic traits (e.g. BRCA1 or 2 mutations) and or strong family history. Effective breast cancer prevention available for high-risk women (drugs or surgery) are hormonal interventions; the strongest basis for breast cancer prevention among high risk women is through hormonal intervention. However, both surgical and drug based prevention have serious negative long term consequences that may not be acceptable to many women. We propose a preventive exercise intervention for increased risk women that might address the same hormonal issues, yet have fewer serious side effects and not impact negatively on quality of life. Exercise training also has many well established positive health benefits beyond those hypothesized herein. These women are highly motivated to reduce their risk. Therefore, even if the alteration in risk is marginal (e.g. consistent with smaller tumor size, delayed onset of breast cancer, or reduced breast density that would improve the success of early screening), women at increased risk deserve to know what they can reasonably expect from regular exercise with regard to reducing breast cancer risk. The overarching goal of the proposed dose response trial is to establish the effects of 5 months of low or high dose exercise on variables known to be associated with breast mitotic activity, among a cohort of 160 women with a > 18 percent lifetime risk for breast cancer. The exercise doses were chosen to approximate the current public health guidelines for health promotion (150 minutes weekly) and weight control (300 minutes weekly). The primary hypothesis to be tested is that exercise training will result in a significant decrease of estrogen exposure, and in a dose response manner. The measurement of estrogen exposure is a particular innovation of the proposed work compared to prior studies that have examined the effects of exercise on estrogens. Daily spot urinary samples will be collected over 2 menstrual cycles before and after the exercise training intervention and the primary outcome will be total hormone exposure as assessed by estrogen area under the curve. Study measures include known mitogens (e.g. daily urinary estrogen and progesterone over multiple menstrual cycles; estrogen metabolites; other sex steroid hormones), as well as fibroglandular tissue volume from MRI scans (as a surrogate of breast mitotic activity). Changes in body composition and adipokines will also be assessed. In combination with data from an ongoing parallel trial in low risk women (the WISER study), the proposed work will provide novel information regarding differences, or lack thereof, in levels of commonly accepted risk factors for breast cancer (estrogens, estrogen metabolism, other sex steroid hormones, adipokines, and body composition), as well as comparisons of the effects of exercise training on these outcomes. PUBLIC HEALTH RELEVANCE: WISER Sister is a randomized controlled trial that will add significantly to understanding the potential for five months of exercise training to reduce breast cancer risk factors (including estrogens and MRI breast imaging) in 160 young women (aged 18-35) with significantly increased risk. In combination with data from an ongoing parallel trial in low risk women (the WISER study), the proposed work will provide novel information regarding differences, or lack thereof, in levels of commonly accepted risk factors for breast cancer (estrogens, breast density from MRI, estrogen metabolism, other steroid hormones, adipokines, and body composition), as well as comparisons of the effects of exercise training on these outcomes. The WISER Sister study will randomize 160 young women with elevated breast cancer risk into 3 equal sized groups: wait list control, low dose exercise (150 minutes weekly, to approximate the current public health recommendations for exercise for general health promotion), and high dose exercise (building to 300 minutes weekly, to approximate the public health recommendations for weight control).




Obesity and metabolic dysfunction correlate with background parenchymal enhancement in premenopausal women.
Authors: Brown J.C. , Ligibel J.A. , Crane T.E. , Kontos D. , Yang S. , Conant E.F. , Mack J.A. , Ahima R.S. , Schmitz K.H. .
Source: Obesity (silver Spring, Md.), 2023 Feb; 31(2), p. 479-486.
EPub date: 2023-01-11 00:00:00.0.
PMID: 36628617
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Association of Inflammatory Diets with Inflammatory Biomarkers in Women at High Genetic Risk for Breast Cancer.
Authors: Boyer A.L. , Arikawa A.Y. , Schmitz K.H. , Sturgeon K.M. .
Source: Nutrition And Cancer, 2022; 74(3), p. 816-819.
EPub date: 2021-10-06 00:00:00.0.
PMID: 34615429
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Dose-dependent effects of aerobic exercise on clinically relevant biomarkers among healthy women at high genetic risk for breast cancer: A secondary analysis of a randomized controlled study.
Authors: Ehret C.J. , Zhou S. , Tchou J.C. , Schmitz K.H. , Sturgeon K.M. .
Source: Cancer Reports (hoboken, N.j.), 2021-07-09 00:00:00.0; , p. e1497.
EPub date: 2021-07-09 00:00:00.0.
PMID: 34240819
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Increased Duration of Exercise Decreases Rate of Nonresponse to Exercise but May Not Decrease Risk for Cancer Mortality.
Authors: Lin D. , Potiaumpai M. , Schmitz K. , Sturgeon K. .
Source: Medicine And Science In Sports And Exercise, 2020-10-08 00:00:00.0; , .
EPub date: 2020-10-08 00:00:00.0.
PMID: 33044435
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Dose-dependent effect of aerobic exercise on inflammatory biomarkers in a randomized controlled trial of women at high risk of breast cancer.
Authors: Haley J.S. , Hibler E.A. , Zhou S. , Schmitz K.H. , Sturgeon K.M. .
Source: Cancer, 2019-09-30 00:00:00.0; , .
EPub date: 2019-09-30 00:00:00.0.
PMID: 31568587
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The dose-response effects of aerobic exercise on musculoskeletal injury: a post hoc analysis of a randomized trial.
Authors: Brown J.C. , Schmitz K.H. .
Source: Research In Sports Medicine (print), 2017 Jul-Sep; 25(3), p. 277-289.
EPub date: 2017-04-06 00:00:00.0.
PMID: 28385043
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Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.
Authors: Sturgeon K. , Digiovanni L. , Good J. , Salvatore D. , Fenderson D. , Domchek S. , Stopfer J. , Galantino M.L. , Bryan C. , Hwang W.T. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 08; 25(8), p. 1195-200.
EPub date: 2016-05-13 00:00:00.0.
PMID: 27197293
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The Dose-Response Effects of Aerobic Exercise on Body Composition and Breast Tissue among Women at High Risk for Breast Cancer: A Randomized Trial.
Authors: Brown J.C. , Kontos D. , Schnall M.D. , Wu S. , Schmitz K.H. .
Source: Cancer Prevention Research (philadelphia, Pa.), 2016 Jul; 9(7), p. 581-8.
PMID: 27099272
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Dose-response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial.
Authors: Schmitz K.H. , Williams N.I. , Kontos D. , Domchek S. , Morales K.H. , Hwang W.T. , Grant L.L. , DiGiovanni L. , Salvatore D. , Fenderson D. , et al. .
Source: Breast Cancer Research And Treatment, 2015 Nov; 154(2), p. 309-18.
PMID: 26510851
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Women In Steady Exercise Research (WISER) Sister: study design and methods.
Authors: Schmitz K.H. , Williams N.I. , Kontos D. , Kurzer M.S. , Schnall M. , Domchek S. , Stopfer J. , Galantino M.L. , Hwang W.T. , Morales K. , et al. .
Source: Contemporary Clinical Trials, 2015 Mar; 41, p. 17-30.
PMID: 25559914
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The effects of aerobic exercise on estrogen metabolism in healthy premenopausal women.
Authors: Smith A.J. , Phipps W.R. , Thomas W. , Schmitz K.H. , Kurzer M.S. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2013 May; 22(5), p. 756-64.
PMID: 23652373
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Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer.
Authors: Kossman D.A. , Williams N.I. , Domchek S.M. , Kurzer M.S. , Stopfer J.E. , Schmitz K.H. .
Source: Journal Of Applied Physiology (bethesda, Md. : 1985), 2011 Dec; 111(6), p. 1687-93.
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Sixteen weeks of exercise reduces C-reactive protein levels in young women.
Authors: Arikawa A.Y. , Thomas W. , Schmitz K.H. , Kurzer M.S. .
Source: Medicine And Science In Sports And Exercise, 2011 Jun; 43(6), p. 1002-9.
PMID: 21085036
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Effects of aerobic exercise on premenopausal sex hormone levels: results of the WISER study, a randomized clinical trial in healthy, sedentary, eumenorrheic women.
Authors: Smith A.J. , Phipps W.R. , Arikawa A.Y. , O'Dougherty M. , Kaufman B. , Thomas W. , Schmitz K.H. , Kurzer M.S. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2011 Jun; 20(6), p. 1098-106.
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No effect of exercise on insulin-like growth factor-I, insulin, and glucose in young women participating in a 16-week randomized controlled trial.
Authors: Arikawa A.Y. , Kurzer M.S. , Thomas W. , Schmitz K.H. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2010 Nov; 19(11), p. 2987-90.
PMID: 20833973
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Women in Steady Exercise Research (WISER): study design and methods.
Authors: Arikawa A.Y. , O'Dougherty M. , Kaufman B.C. , Smith A.J. , Thomas W. , Warren M. , Kurzer M.S. , Schmitz K.H. .
Source: Contemporary Clinical Trials, 2010 Sep; 31(5), p. 457-65.
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