title: Lifestyle intervention in BRCA1/2 mutation carriers: study protocol for a prospective, randomized, controlled clinical feasibility trial (LIBRE-1 study).
abstract: BACKGROUND
  Women with highly penetrant BRCA mutations have a 55-60% lifetime risk for breast cancer and a 16-59% lifetime risk for ovarian cancer. However, penetrance differs interindividually, indicating that environmental and behavioral factors may modify this risk. These include lifestyle factors such as physical activity status, dietary habits, and body weight. The modification of penetrance by changing lifestyle factors has not thus far been investigated in a randomized trial in BRCA mutation carriers.
  
  
  METHODS
  Therefore, we intend to enroll 60 BRCA1/2 mutation carriers in a pilot feasibility study (Lifestyle Intervention Study in Women with Hereditary Breast and Ovarian Cancer (LIBRE) pilot). This multi-center, prospective, controlled trial aims to randomize (1:1) participants into a (1) multi-factorial lifestyle intervention group (IG) versus (2) the control group with usual care (CG). The primary endpoint is feasibility and acceptance of a structured interdisciplinary lifestyle intervention program over 12 months (at least 70% of the patients to complete the 1-year intervention). Furthermore, the effects on physical fitness, BMI, quality of life, and stress coping capacity will be investigated. During the first 3 months, women in the IG will receive structured, individualized and mainly supervised endurance training of ≥18 MET*h/week (MET = metabolic equivalent task) and personal nutritional counseling based on the Mediterranean diet. During the subsequent 9 months, the IG will receive monthly group training sessions and regular telephone contacts for motivation, whereas the CG will only receive usual care (one general counseling on healthy nutrition and benefits of regular physical activity on health status). At randomization and subsequent time points (3, 6, 12 months), cardiopulmonary fitness will be assessed by spiroergometry and nutritional and psychological status by validated questionnaires.
  
  
  CONCLUSIONS
  This pilot study will investigate the optimal strategy to improve physical fitness, nutritional habits, and psychological factors in women at high risk for developing breast or ovarian cancer. The results of this pilot feasibility study will be the basis for a larger prospective randomized trial including clinical events (LIBRE).
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT02087592.
authors.affiliation: Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Marion
authors.identifier: 0000-0003-4237-2657
authors.initials: M
authors.lastname: Kiechle
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
authors.affiliation: Department of Prevention and Sports Medicine, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany ; Else Kroener-Fresenius Prevention Center, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Berling
authors.affiliation: Institute for Nutritional Medicine, University Hohenheim, Fruwirthstr. 12, 70593 Stuttgart, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hebestreit
authors.affiliation: Institute for Nutritional Medicine, University Hohenheim, Fruwirthstr. 12, 70593 Stuttgart, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bischoff
authors.affiliation: Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Dukatz
authors.affiliation: Institute for Medical Psychology and Sociology, University Hospital Schleswig-Holstein, Campus Kiel, Preusserstr. 1-9, 24105 Kiel, Germany.
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Gerber
authors.affiliation: Institute for Medical Psychology and Sociology, University Hospital Schleswig-Holstein, Campus Kiel, Preusserstr. 1-9, 24105 Kiel, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Siniatchkin
authors.affiliation: Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Pfeifer
authors.affiliation: Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Grill
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany.
authors.forename: Maryam
authors.initials: M
authors.lastname: Yahiaoui-Doktor
authors.affiliation: Institute for Medical Psychology and Sociology, University Hospital Schleswig-Holstein, Campus Kiel, Preusserstr. 1-9, 24105 Kiel, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kirsch
authors.affiliation: Institute for Medical Psychology and Sociology, University Hospital Schleswig-Holstein, Campus Kiel, Preusserstr. 1-9, 24105 Kiel, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Niederberger
authors.affiliation: Institute for Medical Psychology and Sociology, University Hospital Schleswig-Holstein, Campus Kiel, Preusserstr. 1-9, 24105 Kiel, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Marter
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Enders
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Löffler
authors.affiliation: Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.affiliation: Center for Hereditary Breast and Ovarian Cancer, University Hospital Cologne, Kerpener Str. 34, 50931 Cologne, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Rhiem
authors.affiliation: Center for Hereditary Breast and Ovarian Cancer, University Hospital Cologne, Kerpener Str. 34, 50931 Cologne, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Schmutzler
authors.affiliation: Department of Prevention and Sports Medicine, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany ; Else Kroener-Fresenius Prevention Center, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Erickson
authors.affiliation: Department of Prevention and Sports Medicine, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany ; Else Kroener-Fresenius Prevention Center, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Halle
keywords: BRCA1; BRCA2; Hereditary breast cancer; Hereditary ovarian cancer; Lifestyle intervention