Effects of lifestyle intervention in BRCA1/2 mutation carriers on nutrition, BMI, and physical fitness (LIBRE study): study protocol for a randomized controlled trial

Marion Kiechle, Christoph Engel, Anika Berling, Katrin Hebestreit, Stephan C Bischoff, Ricarda Dukatz, Michael Siniatchkin, Katharina Pfeifer, Sabine Grill, Maryam Yahiaoui-Doktor, Ellen Kirsch, Uwe Niederberger, Ute Enders, Markus Löffler, Alfons Meindl, Kerstin Rhiem, Rita Schmutzler, Nicole Erickson, Martin Halle, Marion Kiechle, Christoph Engel, Anika Berling, Katrin Hebestreit, Stephan C Bischoff, Ricarda Dukatz, Michael Siniatchkin, Katharina Pfeifer, Sabine Grill, Maryam Yahiaoui-Doktor, Ellen Kirsch, Uwe Niederberger, Ute Enders, Markus Löffler, Alfons Meindl, Kerstin Rhiem, Rita Schmutzler, Nicole Erickson, Martin Halle

Abstract

Background: Women with highly penetrant BRCA mutations have a 55-60 % lifetime risk for breast cancer and a 16-59 % lifetime risk of developing ovarian cancer. However, penetrance differs interindividually, indicating that environmental and behavioral factors may modify this risk. It is well documented that the risk for sporadic breast cancer disease can be modified by changing lifestyle factors that primarily include physical activity, dietary habits, and body weight. It can thus be hypothesized that the modification of these lifestyle factors may also influence the incidence and progression of cancer in BRCA mutation carriers.

Methods/design: This multicenter, interdisciplinary, prospective, two-armed, randomized (1:1) controlled trial aims to enroll a minimum of 600 BRCA1 and BRCA2 mutation carriers to partake in either a lifestyle intervention or usual care. The study primarily aims to demonstrate an improvement of nutritional behavior (adherence to the Mediterranean diet), body mass index, and physical fitness. Furthermore, the effects on quality of life, stress coping capacity, breast cancer incidence, and mortality will be investigated. The intervention group (IG) will receive a structured lifestyle intervention over 12 months, whereas the control group (CG) will only receive information regarding a healthy lifestyle. During the first 3 months, women in the IG will receive structured, individualized, and mainly supervised endurance training with a minimum of 18 MET-h physical activity per week and nutrition education based on the Mediterranean diet. Over the following 9 months, IG monthly group training sessions and regular telephone contacts will motivate study participants. The CG will receive one general training session about healthy nutrition in accordance with the recommendations of the German Society of Nutrition (standard of care in Germany) and the benefits of regular physical activity on health status. At randomization and subsequent time points (3 and 12 months), cardiopulmonary fitness will be assessed by spiroergometry, and nutritional and psychological status will be assessed by validated questionnaires, interviews, and clinical examinations.

Discussion: As data on the role of lifestyle intervention in women with a hereditary risk for breast and ovarian cancer are currently lacking, this study will be of major importance from a scientific, as well as a practical advice viewpoint. It will investigate the optimal strategy to improve physical fitness, nutritional status, and psychological factors such as quality of life, perceived stress, optimism, as well as incidence and outcome of cancer in this selected group of women at high risk. If the study indicates a positive long-term outcome, a structured lifestyle intervention program could be added to health care prevention strategies for BRCA1 and BRCA2 mutation carriers.

Trial registration: ClinicalTrials.gov: NCT02516540 . Registered on 22 July 2015.

Keywords: BRCA1; BRCA2; Hereditary breast cancer; Hereditary ovarian cancer; Lifestyle intervention.

Figures

Fig. 1
Fig. 1
Design of the trial

References

    1. Mavaddat N, Pharoah PD, Michailidou K, et al. Prediction of breast cancer risk based on profiling with common genetic variants. J Natl Cancer Inst. 2015;107
    1. Mavaddat N, Peock S, Frost D, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst. 2013;105:812–22. doi: 10.1093/jnci/djt095.
    1. Easton DF, Pharoah PD, Antoniou AC, et al. Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med. 2015;372:2243–57. doi: 10.1056/NEJMsr1501341.
    1. Antoniou AC, Kuchenbaecker KB, Soucy P, et al. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. Breast Cancer Res. 2012;14:R33. doi: 10.1186/bcr3121.
    1. Bissonauth V, Shatenstein B, Fafard E, et al. Weight history, smoking, physical activity and breast cancer risk among French-Canadian women non-carriers of more frequent BRCA1/2 mutations. J Cancer Epidemiol. 2009;2009:748367. doi: 10.1155/2009/748367.
    1. Pettapiece-Phillips R, Narod SA, Kotsopoulos J. The role of body size and physical activity on the risk of breast cancer in BRCA mutation carriers. Cancer Causes Control. 2015;26:333–44. doi: 10.1007/s10552-014-0521-0.
    1. Friedenreich CM, Woolcott CG, McTiernan A, et al. Alberta physical activity and breast cancer prevention trial: sex hormone changes in a year-long exercise intervention among postmenopausal women. J Clin Oncology. 2010;28:1458–66. doi: 10.1200/JCO.2009.24.9557.
    1. Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA. Physical activity and survival after breast cancer diagnosis. JAMA. 2005;293:2479–86. doi: 10.1001/jama.293.20.2479.
    1. Backman M, Wengstrom Y, Johansson B, et al. A randomized pilot study with daily walking during adjuvant chemotherapy for patients with breast and colorectal cancer. Acta Oncol. 2014;53:510–20. doi: 10.3109/0284186X.2013.873820.
    1. Rosato V, Bosetti C, Talamini R, et al. Metabolic syndrome and the risk of breast cancer in postmenopausal women. Ann Oncology. 2011;22:2687–92. doi: 10.1093/annonc/mdr025.
    1. Ewertz M, Jensen MB, Gunnarsdottir KA, et al. Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncology. 2011;29:25–31. doi: 10.1200/JCO.2010.29.7614.
    1. Chlebowski RT, Blackburn GL, Thomson CA, et al. Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women’s Intervention Nutrition Study. J Natl Cancer Inst. 2006;98:1767–76. doi: 10.1093/jnci/djj494.
    1. Toledo E, Salas-Salvado J, Donat-Vargas C, et al. Mediterranean diet and invasive breast cancer risk among women at high cardiovascular risk in the PREDIMED Trial: a randomized clinical trial. JAMA Internal Med. 2015;175:1752–60. doi: 10.1001/jamainternmed.2015.4838.
    1. Antoni MH, Lutgendorf SK, Blomberg B, et al. Cognitive-behavioral stress management reverses anxiety-related leukocyte transcriptional dynamics. Biol Psychiatry. 2012;71:366–72. doi: 10.1016/j.biopsych.2011.10.007.
    1. Antoni MH, Lechner S, Diaz A, et al. Cognitive behavioral stress management effects on psychosocial and physiological adaptation in women undergoing treatment for breast cancer. Brain Behav Immun. 2009;23:580–91. doi: 10.1016/j.bbi.2008.09.005.
    1. Phillips KM, Antoni MH, Lechner SC, et al. Stress management intervention reduces serum cortisol and increases relaxation during treatment for nonmetastatic breast cancer. Psychosom Med. 2008;70:1044–9. doi: 10.1097/PSY.0b013e318186fb27.
    1. Culver JL, Arena PL, Antoni MH, Carver CS. Coping and distress among women under treatment for early stage breast cancer: comparing African Americans, Hispanics and non-Hispanic Whites. Psychooncology. 2002;11:495–504. doi: 10.1002/pon.615.
    1. Wimberly SR, Carver CS, Antoni MH. Effects of optimism, interpersonal relationships, and distress on psychosexual well-being among women with early stage breast cancer. Psychol Health. 2008;23:57–72. doi: 10.1080/14768320701204211.
    1. Courneya KS, McKenzie DC, Mackey JR, et al. Subgroup effects in a randomised trial of different types and doses of exercise during breast cancer chemotherapy. Br J Cancer. 2014;111:1718–25. doi: 10.1038/bjc.2014.466.
    1. Manders P, Pijpe A, Hooning MJ, et al. Body weight and risk of breast cancer in BRCA1/2 mutation carriers. Breast Cancer Res Treat. 2011;126:193–202. doi: 10.1007/s10549-010-1120-8.
    1. Van Holle V, De Bourdeaudhuij I, Deforche B, Van Cauwenberg J, Van Dyck D. Assessment of physical activity in older Belgian adults: validity and reliability of an adapted interview version of the long International Physical Activity Questionnaire (IPAQ-L) BMC Public Health. 2015;15:433. doi: 10.1186/s12889-015-1785-3.
    1. Grimm EK, Swartz AM, Hart T, Miller NE, Strath SJ. Comparison of the IPAQ-Short Form and accelerometry predictions of physical activity in older adults. J Aging Phys Act. 2012;20:64–79.
    1. Guazzi M, Adams V, Conraads V, et al. EACPR/AHA Scientific Statement. Clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations. Circulation. 2012;126:2261–74. doi: 10.1161/CIR.0b013e31826fb946.
    1. Hallal PC, Victora CG. Reliability and validity of the International Physical Activity Questionnaire (IPAQ) Med Sci Sports Exerc. 2004;36:556. doi: 10.1249/01.MSS.0000117161.66394.07.
    1. Boeing H, Bohlscheid-Thomas S, Voss S, Schneeweiss S, Wahrendorf J. The relative validity of vitamin intakes derived from a food frequency questionnaire compared to 24-hour recalls and biological measurements: results from the EPIC pilot study in Germany. European Prospective Investigation into Cancer and Nutrition. Int J Epidemiol. 1997;26 Suppl 1:S82–90. doi: 10.1093/ije/26.suppl_1.S82.
    1. Bohlscheid-Thomas S, Hoting I, Boeing H, Wahrendorf J. Reproducibility and relative validity of energy and macronutrient intake of a food frequency questionnaire developed for the German part of the EPIC project. European Prospective Investigation into Cancer and Nutrition. Int J Epidemiol. 1997;26 Suppl 1:S71–81. doi: 10.1093/ije/26.suppl_1.S71.
    1. Kroke A, Klipstein-Grobusch K, Voss S, et al. Validation of a self-administered food-frequency questionnaire administered in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study: comparison of energy, protein, and macronutrient intakes estimated with the doubly labeled water, urinary nitrogen, and repeated 24-h dietary recall methods. Am J Clin Nutr. 1999;70:439–47.
    1. Schroder H, Fito M, Estruch R, et al. A short screener is valid for assessing Mediterranean diet adherence among older Spanish men and women. J Nutr. 2011;141:1140–5. doi: 10.3945/jn.110.135566.
    1. Sprangers MA, Groenvold M, Arraras JI, et al. The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study. J Clin Oncology. 1996;14:2756–68.
    1. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–76. doi: 10.1093/jnci/85.5.365.
    1. Scott NW, Fayers PM, Aaronson NK, Bottomley A, de Graeff A, Groenvold M, Gundy C, Koller M, Petersen MA, Sprangers MAG, on behalf of the EORTC Quality of Life Group . EORTC QLQ-C30 reference values. Brussels, Belgium: EORTC Quality of Life Group Publications; 2008.
    1. Oliveira IS, da Cunha Menezes Costa L, Fagundes FR, Cabral CM. Evaluation of cross-cultural adaptation and measurement properties of breast cancer-specific quality-of-life questionnaires: a systematic review. Qual Life Res. 2015;24:1179–95. doi: 10.1007/s11136-014-0840-3.
    1. Glaesmer H, Hoyer J, Klotsche J, Herzberg Y. Die deutsche Version des Life Orientation Tests (LOT-R) zum dispositionellen Optimismus und Pessimismus. Zeitschrift für Gesundheitspsychologie. 2008;16
    1. Schulz P, Becker P, Schlotz W. TICS: Trierer Inventar zum chronischen Stress: Manual. Göttingen, Germany: Hogrefe; 2004.
    1. Fishbein M, Ajzen I. Belief, attitude, intention, and behavior. An introduction to theory and research. Addison-Wesley series in social psychology. Reading, MA: Addison-Wesley Publishing Company; 1975.
    1. Vallance JK, Courneya KS, Plotnikoff RC, Dinu I, Mackey JR. Maintenance of physical activity in breast cancer survivors after a randomized trial. Med Sci Sports Exerc. 2008;40:173–80. doi: 10.1249/mss.0b013e3181586b41.
    1. Vallance JK, Courneya KS, Plotnikoff RC, Mackey JR. Analyzing theoretical mechanisms of physical activity behavior change in breast cancer survivors: results from the activity promotion (ACTION) trial. Ann Behav Med. 2008;35:150–8. doi: 10.1007/s12160-008-9019-x.
    1. Armitage CJ. Can the theory of planned behavior predict the maintenance of physical activity? Health Psychol. 2005;24:235–45. doi: 10.1037/0278-6133.24.3.235.
    1. Sivell S, Elwyn G, Edwards A, Manstead AS. Factors influencing the surgery intentions and choices of women with early breast cancer: the predictive utility of an extended theory of planned behaviour. BMC Med Inform Decis Mak. 2013;13:92. doi: 10.1186/1472-6947-13-92.
    1. Blanchard CM, Fisher J, Sparling PB, et al. Understanding adherence to 5 servings of fruits and vegetables per day: a theory of planned behavior perspective. J Nutr Educ Behav. 2009;41:3–10. doi: 10.1016/j.jneb.2007.12.006.
    1. Pocock SJ. Clinical trials—a practical approach. Chichester, NY: John Wiley & Sons; 1983.
    1. Pasanisi P, Bruno E, Manoukian S, Berrino F. A randomized controlled trial of diet and physical activity in BRCA mutation carriers. Fam Cancer. 2014;13(2):181–7. doi: 10.1007/s10689-013-9691-2.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi