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Breast Cancer Research and Treatment

, Volume 126, Issue 1, pp 193–202 | Cite as

Body weight and risk of breast cancer in BRCA1/2 mutation carriers

  • Peggy Manders
  • Anouk Pijpe
  • Maartje J. Hooning
  • Irma Kluijt
  • Hans F. A. Vasen
  • Nicoline Hoogerbrugge
  • Christi J. van Asperen
  • Hanne Meijers-Heijboer
  • Margreet G. E. M. Ausems
  • Theo A. van Os
  • Encarna B. Gomez-Garcia
  • Richard M. Brohet
  • HEBON
  • Flora E. van Leeuwen
  • Matti A. RookusEmail author
Epidemiology

Abstract

Obesity is an established risk factor for postmenopausal breast cancer in the general population. However, it is still unclear whether this association also exists in BRCA1/2 mutation carriers. We investigated the association between self-reported anthropometric measures and breast cancer risk in a nationwide retrospective cohort study, including 719 BRCA1/2 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. All time-varying Cox proportional hazards analyses were stratified by menopausal status. For premenopausal breast cancer, no statistically significant associations were observed for any of the anthropometric measures. The association between body mass index (BMI) at age 18 and premenopausal breast cancer risk suggested a trend of decreasing risk with increasing BMI (HR22.50–24.99 vs. 18.50–22.49 = 0.83, 95% CI = 0.47–1.44 and HR≥25.00 vs. 18.50–22.49 = 0.41, 95% CI = 0.13–1.27). For postmenopausal breast cancer, being 1.67 m and taller increased the risk 1.7-fold (HR = 1.67, 95% CI = 1.01–2.74) when compared to a height <1.67 m. Compared with a current body weight <72 kg, a current body weight of ≥72 kg increased the risk of postmenopausal breast cancer 2.1-fold (95% CI = 1.23–3.59). A current BMI of ≥25.0 kg/m2, an adult weight gain of 5 kg or more, and a relative adult weight gain of 20% or more were all non-significantly associated with a 50–60% increased risk of postmenopausal breast cancer [HR = 1.46 (0.86–2.51), HR = 1.56 (95% CI = 0.85–2.87), and HR = 1.60 (95% CI = 0.97–2.63), respectively], when compared with having a healthy or stable weight. No associations for body weight or BMI at age 18 were observed. In conclusion, menopausal status seemed to modify the association between body weight and breast cancer risk among BRCA1/2 carriers. We observed no clear association between body weight and premenopausal breast cancer, while overweight and weight gain increased postmenopausal breast cancer risk. Carriers may reduce their risk of postmenopausal breast cancer by maintaining a healthy body weight throughout life.

Keywords

Body weight Breast cancer BRCA1/2 HEBON Epidemiology 

Notes

Acknowledgments

This work was financially supported by the Dutch Cancer Society (grants NKI1998-1854, NKI2004-3088, NKI 2007-3756).

References

  1. 1.
    Antoniou AC, Gayther SA, Stratton JF, Ponder BA, Easton DF (2000) Risk models for familial ovarian and breast cancer. Genet Epidemiol 18(2):173–190CrossRefPubMedGoogle Scholar
  2. 2.
    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(18):1365–1372CrossRefPubMedGoogle Scholar
  3. 3.
    Fodor FH, Weston A, Bleiweiss IJ et al (1998) Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients. Am J Hum Genet 63(1):45–51CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Risch HA, McLaughlin JR, Cole DE et al (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68(3):700–710CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Thompson D, Easton D (2001) Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet 68(2):410–419CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Warner E, Foulkes W, Goodwin P et al (1999) Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer. J Natl Cancer Inst 91(14):1241–1247CrossRefPubMedGoogle Scholar
  7. 7.
    Couch FJ, Weber BL (1996) Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Breast Cancer Information Core. Hum Mutat 8(1):8–18CrossRefPubMedGoogle Scholar
  8. 8.
    Shattuck-Eidens D, Oliphant A, McClure M et al (1997) BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing. JAMA 278(15):1242–1250CrossRefPubMedGoogle Scholar
  9. 9.
    Breast Cancer Information Core (BIC) http://research.nhgri.nih.gov/bic/. Accessed 8 Feb 2010
  10. 10.
    Antoniou AC, Spurdle AB, Sinilnikova OM et al (2008) Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet 82(4):937–948CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Meijers-Heijboer H, van den Ouweland A, Klijn J et al (2002) Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31(1):55–59CrossRefPubMedGoogle Scholar
  12. 12.
    Rebbeck TR, Kantoff PW, Krithivas K et al (1999) Modification of BRCA1-associated breast cancer risk by the polymorphic androgen-receptor CAG repeat. Am J Hum Genet 64(5):1371–1377CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Narod SA (2006) Modifiers of risk of hereditary breast cancer. Oncogene 25(43):5832–5836CrossRefPubMedGoogle Scholar
  14. 14.
    Antoniou A, Pharoah PD, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646CrossRefPubMedGoogle Scholar
  16. 16.
    Narod S, Lynch H, Conway T, Watson P, Feunteun J, Lenoir G (1993) Increasing incidence of breast cancer in family with BRCA1 mutation. Lancet 341(8852):1101–1102CrossRefPubMedGoogle Scholar
  17. 17.
    Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4(8):579–591CrossRefPubMedGoogle Scholar
  18. 18.
    Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578CrossRefPubMedGoogle Scholar
  19. 19.
    World Cancer Research Fund/American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. IARC, Washington DCGoogle Scholar
  20. 20.
    Chang-Claude J, Becher H, Eby N, Bastert G, Wahrendorf J, Hamann U (1997) Modifying effect of reproductive risk factors on the age at onset of breast cancer for German BRCA1 mutation carriers. J Cancer Res Clin Oncol 123(5):272–279PubMedGoogle Scholar
  21. 21.
    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(3):285–294CrossRefPubMedGoogle Scholar
  22. 22.
    Kotsopoulos J, Olopado OI, Ghadirian P et al (2005) Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res 7(5):R833–R843CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Pijpe A, Manders P, Brohet RM et al (2010) Physical activity and the risk of breast cancer in BRCA1/2 mutation carriers. Breast Cancer Res Treat 120(1):235–244CrossRefPubMedGoogle Scholar
  24. 24.
    Abrahamson PE, Gammon MD, Lund MJ et al (2006) General and abdominal obesity and survival among young women with breast cancer. Cancer Epidemiol Biomarkers Prev 15(10):1871–1877CrossRefPubMedGoogle Scholar
  25. 25.
    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348(17):1625–1638CrossRefPubMedGoogle Scholar
  26. 26.
    Koster A, Harris TB, Moore SC et al (2009) Joint associations of adiposity and physical activity with mortality: the National Institutes of Health-AARP Diet and Health Study. Am J Epidemiol 169(11):1344–1351CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Carmichael AR (2006) Obesity and prognosis of breast cancer. Obes Rev 7(4):333–340CrossRefPubMedGoogle Scholar
  28. 28.
    Cleveland RJ, Eng SM, Abrahamson PE et al (2007) Weight gain prior to diagnosis and survival from breast cancer. Cancer Epidemiol Biomarkers Prev 16(9):1803–1811CrossRefPubMedGoogle Scholar
  29. 29.
    Kellen E, Vansant G, Christiaens MR, Neven P, Van LE (2009) Lifestyle changes and breast cancer prognosis: a review. Breast Cancer Res Treat 114(1):13–22CrossRefPubMedGoogle Scholar
  30. 30.
    Andrieu N, Goldgar DE, Easton DF et al (2006) Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS). J Natl Cancer Inst 98(8):535–544CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Andrieu N, Easton DF, Chang-Claude J et al (2006) Effect of chest X-rays on the risk of breast cancer among BRCA1/2 mutation carriers in the international BRCA1/2 carrier cohort study: a report from the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators’ Group. J Clin Oncol 24(21):3361–3366CrossRefPubMedGoogle Scholar
  32. 32.
    Brohet RM, Goldgar DE, Easton DF et al (2007) Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. J Clin Oncol 25(25):3831–3836CrossRefPubMedGoogle Scholar
  33. 33.
    Antoniou AC, Goldgar DE, Andrieu N et al (2005) A weighted cohort approach for analysing factors modifying disease risks in carriers of high-risk susceptibility genes. Genet Epidemiol 29(1):1–11CrossRefPubMedGoogle Scholar
  34. 34.
    WHO Expert Committee (1995) Physical status: the use and interpretation of anthropomerty. WHO technical report series 854Google Scholar
  35. 35.
    Heideman WH, Russell NS, Gundy C, Rookus MA, Voskuil DW (2009) The frequency, magnitude and timing of post-diagnosis body weight gain in Dutch breast cancer survivors. Eur J Cancer 45(1):119–126CrossRefPubMedGoogle Scholar
  36. 36.
    Gorber SC, Tremblay M, Moher D, Gorber B (2007) A comparison of direct vs. self-report measures for assessing height, weight and body mass index: a systematic review. Obes Rev 8(4):307–326CrossRefPubMedGoogle Scholar
  37. 37.
    Rebbeck TR, Kauff ND, Domchek SM (2009) Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 101(2):80–87CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Lakhani SR, Van DV, Jacquemier J et al (2002) The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 20(9):2310–2318CrossRefPubMedGoogle Scholar
  39. 39.
    Hosey AM, Gorski JJ, Murray MM et al (2007) Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer. J Natl Cancer Inst 99(22):1683–1694CrossRefPubMedGoogle Scholar
  40. 40.
    Gorski JJ, Kennedy RD, Hosey AM, Harkin DP (2009) The complex relationship between BRCA1 and ERalpha in hereditary breast cancer. Clin Cancer Res 15(5):1514–1518CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Lahmann PH, Hoffmann K, Allen N et al (2004) Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 111(5):762–771CrossRefPubMedGoogle Scholar
  42. 42.
    van den Brandt PA, Spiegelman D, Yaun SS et al (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152(6):514–527CrossRefPubMedGoogle Scholar
  43. 43.
    Hankinson SE, Willett WC, Colditz GA et al (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351(9113):1393–1396CrossRefPubMedGoogle Scholar
  44. 44.
    Stoll BA (1992) Does extra height justify a higher risk of breast cancer? Ann Oncol 3(1):29–30PubMedGoogle Scholar
  45. 45.
    Willett W (1990) Nutritional epidemiology. Oxford University Press, New YorkGoogle Scholar
  46. 46.
    Ballard-Barbash R (1994) Anthropometry and breast cancer. Body size—a moving target. Cancer 74(3 Suppl):1090–1100CrossRefPubMedGoogle Scholar
  47. 47.
    Trichopoulos D, Lipman RD (1992) Mammary gland mass and breast cancer risk. Epidemiology 3(6):523–526CrossRefPubMedGoogle Scholar
  48. 48.
    Morimoto LM, White E, Chen Z et al (2002) Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative (United States). Cancer Causes Control 13(8):741–751CrossRefPubMedGoogle Scholar
  49. 49.
    Metcalfe KA, Birenbaum-Carmeli D, Lubinski J et al (2008) International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers. Int J Cancer 122(9):2017–2022CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Peggy Manders
    • 1
    • 5
  • Anouk Pijpe
    • 1
  • Maartje J. Hooning
    • 2
  • Irma Kluijt
    • 3
  • Hans F. A. Vasen
    • 4
  • Nicoline Hoogerbrugge
    • 5
  • Christi J. van Asperen
    • 6
  • Hanne Meijers-Heijboer
    • 7
  • Margreet G. E. M. Ausems
    • 8
  • Theo A. van Os
    • 9
  • Encarna B. Gomez-Garcia
    • 10
  • Richard M. Brohet
    • 1
    • 11
  • HEBON
  • Flora E. van Leeuwen
    • 1
  • Matti A. Rookus
    • 1
    Email author
  1. 1.Department of EpidemiologyNetherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Department of Medical OncologyRotterdam Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer CenterRotterdamThe Netherlands
  3. 3.Family Cancer ClinicNetherlands Cancer InstituteAmsterdamThe Netherlands
  4. 4.The Netherlands Foundation for the Detection of Hereditary TumoursPoortgebouw ZuidLeidenThe Netherlands
  5. 5.Department of Human GeneticsRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  6. 6.Department of Clinical GeneticsLeiden University Medical CenterLeidenThe Netherlands
  7. 7.Department of Clinical Genetics and Human GeneticsVU University Medical CenterAmsterdamThe Netherlands
  8. 8.Department of Medical GeneticsUniversity Medical Center UtrechtUtrechtThe Netherlands
  9. 9.Department of Clinical GeneticsAcademic Medical CenterAmsterdamThe Netherlands
  10. 10.Department of Clinical GeneticsMaastricht University Medical CenterMaastrichtThe Netherlands
  11. 11.Department of Research and EducationSpaarne HospitalHoofddorpThe Netherlands

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