Skip to main content

Advertisement

SpringerLink
Log in

A randomized controlled trial of diet and physical activity in BRCA mutation carriers

  • Short Communication
  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

High serum levels of insulin-like growth factor I (IGF-I) are associated with an increased risk of sporadic breast cancer (BC). Furthermore, insulin and markers of insulin resistance, such as abdominal obesity, high blood glucose, high serum testosterone and metabolic syndrome, may affect both BC incidence and prognosis. We hypothesized that all these factors might be relevant also for hereditary BC, due to a deleterious mutation of BRCA genes. Epidemiological observation suggested that weight, energy intake (usually associated with higher bio-availability of growth factors) and physical activity may be relevant in BRCA mutation carriers. Mechanistic studies hypothesized a functional interaction between BRCA genes and the IGF-I system. We have provided some evidence that high serum levels of IGF-I are associated with a significantly increased penetrance. We are recruiting a larger cohort of BRCA mutation carriers in order to test potential modulators of penetrance and prognosis. Within this cohort, we have planned a randomized controlled trial to test whether moderate calorie and protein restriction, together with physical activity, decrease IGF-I. Eligible study subjects are women with or without BC, aged 18–70, with a proven deleterious BRCA mutation, and without metastases. All the women will receive recommendations for the dietary prevention of cancer. The women will be then randomized into an active life-style intervention group and into a control group that will receive only the baseline recommendations. We expect to significantly reduce IGF-I in the intervention group. This trial and the subsequent cohort follow-up might open up primary prevention options for genetic BC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Campagnoli C, Pasanisi P, Peris C, Berrino F (2008) Insulin-like growth factor-I and breast cancer: epidemiological and clinical data. In: Pasqualini JR (ed) Breast cancer: prognosis, treatment and prevention, 2nd edn. INFORMA-Healthcare, New York

    Google Scholar 

  2. Key TJ, Appleby PN, Reeves GK, Roddam AW (2010) Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 11:530–542

    Article  PubMed  Google Scholar 

  3. Pasanisi P, Villarini A, Raimondi M, Bruno E, Gargano G, Berrino F (2010) Nutritional advice to breast cancer survivors. Support Care Cancer 18:29–33

    Article  Google Scholar 

  4. The Breast Cancer Linkage Consortium (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91:1310–1316

    Google Scholar 

  5. Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL, Weber BL (2002) Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 94:1365–1372

    Article  CAS  PubMed  Google Scholar 

  6. Easton DF, Bishop DT, Ford D, Crockford GP (1993) Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The breast cancer linkage consortium. Am J Hum Genet 52:678–701

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Hopper JL, Southey MC, Dite GS, Jolley DJ, Giles GG, McCredie MR, Easton DF, Venter DJ (1999) Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study. Cancer Epidemiol Biomarkers Prev 8:741–747

    CAS  PubMed  Google Scholar 

  8. Loman N, Bladstrom A, Johannsson O, Borg A, Olsson H (2003) Cancer incidence in relatives of a population-based set of cases of early-onset breast cancer with a known BRCA1 and BRCA2 mutation status. Breast Cancer Res 5:R175–R186

    Article  PubMed Central  PubMed  Google Scholar 

  9. Narod SA (2006) Modifiers of risk of hereditary breast cancer. Oncogene 25:5832–5836

    Article  CAS  PubMed  Google Scholar 

  10. Sellers TA, Davis J, Cerhan JR, Vierkant RA, Olson JE, Pankratz VS, Potter JD, Folsom AR (2002) Interaction of waist/hip ratio and family history on the risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women. Am J Epidemiol 155:225–233

    Article  PubMed  Google Scholar 

  11. Bissonauth V, Shatenstein B, Fafard E, Maugard C, Robidoux A, Narod S, Ghadirian P (2009) Risk of breast cancer among French-Canadian women, noncarriers of more frequent BRCA1/2 mutations and consumption of total energy, coffee, and alcohol. Breast J 15(Suppl 1):S63–S71

    Article  PubMed  Google Scholar 

  12. Kotsopoulos J, Olopado OI, Ghadirian P, Lubinski J, Lynch HT, Isaacs C, Weber B, Kim-Sing C, Ainsworth P, Foulkes WD, Eisen A, Sun P, Narod SA (2005) Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res 7:R833–R843

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Nkondjock A, Robidoux A, Paredes Y, Narod SA, Ghadirian P (2006) Diet, lifestyle and BRCA-related breast cancer risk among French-Canadians. Breast Cancer Res Treat 98:285–294

    Article  CAS  PubMed  Google Scholar 

  14. Manders P, Pijpe A, Hooning MJ, Kluijt I, Vasen HF, Hoogerbrugge N, van Asperen CJ, Meijers-Heijboer H, Ausems MG, van Os TA, Gomez-Garcia EB, Brohet RM, van Leeuwen FE, Rookus MA (2011) Body weight and risk of breast cancer in BRCA1/2 mutation carriers. Breast Cancer Res Treat 126:193–202

    Article  CAS  PubMed  Google Scholar 

  15. Berrino F, Pasanisi P, Berrino J, Curtosi P, Bellati C (2002) A European case-only study on familial breast cancer. IARC Sci Publ 156:63–65

    CAS  PubMed  Google Scholar 

  16. Pasanisi P, Berrino J, Fusconi E, Curtosi PFB (2005) A European case-only study (COS) on familial breast cancer. J Nutr 135:3040S–3041S

    Google Scholar 

  17. Pasanisi P, Hedelin G, Berrino J, Chang-Claude J, Hermann S, Steel M, Haites NE, Hart J, Peled R, Gafà L, Leggio L, Traina A, Amodio R, Primic-Zakelj M, Zadnik V, Veidebaum T, Tekkel M, Berrino F (2009) Oral contraceptive use and BRCA penetrance: a case-only study. Cancer Epidemiol Biomarkers Prev 18:2107–2113

    Article  CAS  PubMed  Google Scholar 

  18. Hoppe C, Molgaard C, Vaag A, Barkholt V, Michaelsen KF (2005) High intakes of milk, but not meat, increase s-insulin and insulin resistance in 8-year-old boys. Eur J Clin Nutr 59:393–398

    Article  CAS  PubMed  Google Scholar 

  19. Norat T, Dossus L, Rinaldi S, Overvad K, Gronbaek H, Tjonneland A, Olsen A, Clavel-Chapelon F, Boutron-Ruault MC, Boeing H, Lahmann PH, Linseisen J, Nagel G, Trichopoulou A, Trichopoulos D, Kalapothaki V, Sieri S, Palli D, Panico S, Tumino R, Sacerdote C, Bueno-De-Mesquita HB, Peeters PH, van Gils CH, Agudo A, Amiano P, Ardanoz E, Martinez C, Quiros R, Tormo MJ, Bingham S, Key TJ, Allen NE, Ferrari P, Slimani N, Riboli E, Kaaks R (2007) Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women. Eur J Clin Nutr 61:91–98

    Article  CAS  PubMed  Google Scholar 

  20. Hudelist G, Wagner T, Rosner M, Fink-Retter A, Gschwantler-Kaulich D, Czerwenka K, Kroiss R, Tea M, Pischinger K, Kostler WJ, Attems J, Mueller R, Blaukopf C, Kubista E, Hengstschlager M, Singer CF (2007) Intratumoral IGF-I protein expression is selectively upregulated in breast cancer patients with BRCA1/2 mutations. Endocr Relat Cancer 14:1053–1062

    Article  CAS  PubMed  Google Scholar 

  21. Maor S, Yosepovich A, Papa MZ, Yarden RI, Mayer D, Friedman E, Werner H (2007) Elevated insulin-like growth factor-I receptor (IGF-IR) levels in primary breast tumors associated with BRCA1 mutations. Cancer Lett 257:236–243

    Article  CAS  PubMed  Google Scholar 

  22. Maor S, Papa MZ, Yarden RI, Friedman E, Lerenthal Y, Lee SW, Mayer D, Werner H (2007) Insulin-like growth factor-I controls BRCA1 gene expression through activation of transcription factor Sp1. Horm Metab Res 39:179–185

    Article  CAS  PubMed  Google Scholar 

  23. Werner H, Bruchim I (2012) IGF-1 and BRCA1 signalling pathways in familial cancer. Lancet Oncol 13:e537–e544

    Article  CAS  PubMed  Google Scholar 

  24. Pasanisi P, Bruno E, Venturelli E, Manoukian S, Barile M, Peissel B, De Giacomi C, Bonanni B, Berrino J, Berrino F (2011) Serum levels of IGF-I and BRCA penetrance: a case control study in breast cancer families. Fam Cancer 10:521–528

    Article  CAS  PubMed  Google Scholar 

  25. World Cancer Research Fund, American Institute for Cancer Research (2007) Food, nutrition, physical activity and the prevention of cancer: a global perspective.Washington DC, AICR

    Google Scholar 

  26. Berrino F, Bellati C, Secreto G, Camerini E, Pala V, Panico S, Allegro G, Kaaks R (2001) Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial. Cancer Epidemiol Biomarkers Prev 10:25–33

    CAS  PubMed  Google Scholar 

  27. Kaaks R, Bellati C, Venturelli E, Rinaldi S, Secreto G, Biessy C, Pala V, Sieri S, Berrino F (2003) Effects of dietary intervention on IGF-I and IGF-binding proteins, and related alterations in sex steroid metabolism: the diet and androgens (DIANA) randomised trial. Eur J Clin Nutr 57:1079–1088

    Article  CAS  PubMed  Google Scholar 

  28. Berryman DE, Christiansen JS, Johannsson G, Thorner MO, Kopchick JJ (2008) Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models. Growth Horm IGF Res 18:455–471

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Fontana L, Klein S, Holloszy JO (2006) Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk. Am J Clin Nutr 84:1456–1462

    CAS  PubMed  Google Scholar 

  30. Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO (2008) Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 7:681–687

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Chen S, Iversen ES, Friebel T, Finkelstein D, Weber BL, Eisen A, Peterson LE, Schildkraut JM, Isaacs C, Peshkin BN, Corio C, Leondaridis L, Tomlinson G, Dutson D, Kerber R, Amos CI, Strong LC, Berry DA, Euhus DM, Parmigiani G (2006) Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol 24:863–871

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Reding KW, Bernstein JL, Langholz BM, Bernstein L, Haile RW, Begg CB, Lynch CF, Concannon P, Borg A, Teraoka SN, Torngren T, Diep A, Xue S, Bertelsen L, Liang X, Reiner AS, Capanu M, Malone KE (2010) Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer. Breast Cancer Res Treat 123:491–498

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Kotsopoulos J, Narod SA (2005) Towards a dietary prevention of hereditary breast cancer. Cancer Causes Control 16:125–138

    Article  PubMed  Google Scholar 

  34. King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302:643–646

    Article  CAS  PubMed  Google Scholar 

  35. Pijpe A, Manders P, Brohet RM, Collee JM, Verhoef S, Vasen HF, Hoogerbrugge N, van Asperen CJ, Dommering C, Ausems MG, Aalfs CM, Gomez-Garcia EB, Van’t Veer LJ, van Leeuwen FE, Rookus MA (2010) Physical activity and the risk of breast cancer in BRCA1/2 mutation carriers. Breast Cancer Res Treat 120:235–244

    Article  PubMed  Google Scholar 

  36. Irwin ML, Varma K, Varez-Reeves M, Cadmus L, Wiley A, Chung GG, Dipietro L, Mayne ST, Yu H (2009) Randomized controlled trial of aerobic exercise on insulin and insulin-like growth factors in breast cancer survivors: the Yale Exercise and Survivorship study. Cancer Epidemiol Biomarkers Prev 18:306–313

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Guinan EM, Hussey J, McGarrigle SA, Healy LA, O’Sullivan JN, Bennett K, Connolly EM (2013) A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene carriers. BMC Cancer 13:138

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Ms Maria Grazia Guerrini for secretarial support and Dr. Maria Teresa Penci for the revision of English.

Author information

Authors and Affiliations

  1. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    P. Pasanisi, E. Bruno & F. Berrino

  2. Medical Genetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    S. Manoukian

Authors
  1. P. Pasanisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Bruno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Manoukian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Berrino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Pasanisi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pasanisi, P., Bruno, E., Manoukian, S. et al. A randomized controlled trial of diet and physical activity in BRCA mutation carriers. Familial Cancer 13, 181–187 (2014). https://doi.org/10.1007/s10689-013-9691-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-013-9691-2

Keywords

Search

Navigation