title: Women In Steady Exercise Research (WISER) Sister: study design and methods.
abstract: OBJECTIVE
  Women at elevated risk for breast cancer are motivated to reduce their risk. Current approaches rely primarily on hormonal intervention. A preventive exercise intervention might address the same hormonal issues, yet have fewer serious side effects and less negative impact on quality of life as compared to prophylactic mastectomy. WISER Sister was a randomized controlled trial which examined effects of two doses of exercise training on endogenous sex hormone exposure, hormonally active breast tissue, and other breast cancer risk factors.
  
  
  METHODS
  Subjects for this single site trial were recruited from across the U.S., in collaboration with organizations that serve women at elevated risk, via emails, flyers, and letters. Eligibility criteria included age ≥ 18, eumenorrheic, and at elevated risk for breast cancer (e.g. BRCA1 or BRCA2 mutation and/or ≥ 18% lifetime risk according to prediction models). A 1:1:1 randomization scheme was used to allocate participants into: control, low dose (150 min/week), or high dose (300 min/week) home based treadmill exercise. Participants provided first morning urine samples daily for two menstrual cycles at study beginning and end for calculation of endogenous hormone exposure. In addition, women completed breast dynamic contrast enhanced magnetic resonance imaging, a fasting blood draw, a treadmill exercise test, and surveys at baseline and follow-up.
  
  
  CONCLUSIONS
  WISER Sister randomized 139 women, 122 of whom completed the study. The overall drop-out rate was 12%. Findings will be useful in understanding the potential for exercise to assist with reducing risk for breast cancer among women at elevated risk.
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA. Electronic address: Schmitz@mail.med.upenn.edu.
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Schmitz
authors.affiliation: Department of Kinesiology, The Penn State University, 276 Recreation Building, University Park, PA 16802, USA.
authors.forename: Nancy I
authors.initials: NI
authors.lastname: Williams
authors.affiliation: Department of Radiology, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, USA.
authors.forename: Despina
authors.initials: D
authors.lastname: Kontos
authors.affiliation: Department of Food Science and Nutrition, 225 FScN, 1334 Eckles Ave, University of Minnesota, St. Paul, MN 55108, USA.
authors.forename: Mindy S
authors.initials: MS
authors.lastname: Kurzer
authors.affiliation: Department of Radiology, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Schnall
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Domchek
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Stopfer
authors.affiliation: Department of Physical Therapy, Richard Stockton College of New Jersey, 101 Vera King Farris Drive, Galloway, NJ 08205-9441, USA.
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Galantino
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hwang
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
authors.forename: Knashawn
authors.initials: K
authors.lastname: Morales
authors.affiliation: Department of Radiology, University of Pittsburgh, 3352 5th Ave, Room 130, Pittsburgh, PA 15213, USA.
authors.forename: Shandong
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: DiGiovanni
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
authors.forename: Domenick
authors.initials: D
authors.lastname: Salvatore
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
authors.forename: Desire'
authors.initials: D
authors.lastname: Fenderson
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
authors.forename: Jerene
authors.initials: J
authors.lastname: Good
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Sturgeon
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
authors.forename: Lorita
authors.initials: L
authors.lastname: Grant
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
authors.forename: Cathy J
authors.initials: CJ
authors.lastname: Bryan
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, 8th floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
authors.forename: Jess
authors.initials: J
authors.lastname: Adelman
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000517:prevention & control*; D004970:Estrone / Q000652:urine; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D020738:Leptin / Q000097:blood; D008279:Magnetic Resonance Imaging; D009154:Mutation; D011276:Pregnanediol / Q000652:urine; D040242:Risk Reduction Behavior; D016896:Treatment Outcome
chemical_list: D052242:Adiponectin; D020738:Leptin; D004970:Estrone; D011276:Pregnanediol
keywords: BRCA mutation; Breast cancer; Exercise; MR imaging; Sex hormones