Breast Cancer Research and Treatment

, Volume 111, Issue 2, pp 329–342 | Cite as

Is obesity an independent prognosis factor in woman breast cancer?

  • Bilal Majed
  • Thierry Moreau
  • Kamel Senouci
  • Rémi J. Salmon
  • Alain Fourquet
  • Bernard Asselain
Epidemiology

Abstract

Background Breast cancer and obesity represent important public health issues in most western countries. A number of studies found a negative prognosis effect of obesity or excess of weight in woman breast cancer. However, to date, this issue remains controversial. The objectives of this study were to confirm the prognosis role of obesity on a large cohort of patients and to investigate a potential independent effect. Materials and methods We constituted a cohort of 14,709 patients who were recruited and treated at the Curie Institute (Paris) from 1981 to 1999. These patients were followed prospectively for a first unilateral invasive breast cancer without distant metastasis. Obesity was defined by a Body Mass Index (BMI) above 30 kg/m2 according to the World Health Organization recommendations. Results Obese patients (8%) presented more extended tumors at diagnosis time suggesting a delayed breast cancer diagnosis. However, obesity appeared as a negative prognosis factor for several events in respectively univariate and multivariate survival analysis: metastasis recurrence (HR = 1.32[1.19–1.48]; HR = 1.12[1.00–1.26]), disease free interval (1.20[1.08–1.32]; 1.10[0.99–1.22]), overall survival (1.43[1.28–1.60]; 1.12[0.99–1.25]) and second primary cancer outcome (1.57[1.19–2.07]; 1.43[1.09–1.89]). Even if obese patients presented more advanced tumors at diagnosis time, multivariate analysis showed that there was a relevant independent effect. Other BMI codings, distinguishing overweight patients or using BMI as a continuous variable, showed a consistent correlation between BMI’s value and prognosis effect. Interaction analysis revealed a more important obesity effect in the presence of tumor estrogen receptors and among limited extent tumors. Conclusions This survey confirms the prognosis role of obesity on one of the largest cohort by investigating several prognosis events. While independent obesity effect linked to hormonal disorders appeared consistent as obesity’s mechanism, we stress that obesity prognosis effect was also related to breast cancer presentation at diagnosis time.

Keywords

Breast cancer Prognosis Obesity Body mass index Survival analysis Interaction analysis 

Notes

Acknowledgements

The author would like to thank Foundation of France (Fondation de France) and FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) for their financial support that permitted this research. The author is also grateful to Chantal Gautier and René ESSER for their constant support.

References

  1. 1.
    Remontet L, Esteve J, Bouvier AM, Grosclaude P, Launoy G, Menegoz F, Exbrayat C, Tretare B, Carli PM, Guizard AV et al (2003) Cancer incidence and mortality in France over the period 1978–2000. Rev Epidemiol Sante Publique 51(1 Pt 1):3–30PubMedGoogle Scholar
  2. 2.
    Centre d’épidémiologie sur les causes de décès. IFR69Google Scholar
  3. 3.
    Prentice AM (2006) The emerging epidemic of obesity in developing countries. Int J Epidemiol 35(1):93–99PubMedCrossRefGoogle Scholar
  4. 4.
    WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 894:i-xii, 1–253Google Scholar
  5. 5.
    Bocquier A, Boullu-Ciocca S, Verger P, Oliver C (2006) Obesity: where are we now? Presse Med 35(2 Pt 2):270–276PubMedCrossRefGoogle Scholar
  6. 6.
    Charles MA (2000) Update on the epidemiology of obesity and type 2 diabetes in France. Diabetes Metab 26(Suppl 3):17–20PubMedGoogle Scholar
  7. 7.
    Goodwin PJ, Boyd NF (1990) Body size and breast cancer prognosis: a critical review of the evidence. Breast Cancer Res Treat 16(3):205–214PubMedCrossRefGoogle Scholar
  8. 8.
    Rock CL, Demark-Wahnefried W (2002) Nutrition and survival after the diagnosis of breast cancer: a review of the evidence. J Clin Oncol 20(15):3302–3316PubMedCrossRefGoogle Scholar
  9. 9.
    Carmichael AR, Bates T (2004) Obesity and breast cancer: a review of the literature. Breast 13(2):85–92PubMedCrossRefGoogle Scholar
  10. 10.
    Carmichael AR (2006) Obesity and prognosis of breast cancer. Obes Rev 7(4):333–340PubMedCrossRefGoogle Scholar
  11. 11.
    Ryu SY, Kim CB, Nam CM, Park JK, Kim KS, Park J, Yoo SY, Cho KS (2001) Is body mass index the prognostic factor in breast cancer?: a meta-analysis. J Korean Med Sci 16(5):610–614PubMedGoogle Scholar
  12. 12.
    Fowble B, Hanlon A, Freedman G, Nicolaou N, Anderson P (2001) Second cancers after conservative surgery and radiation for stages I-II breast cancer: identifying a subset of women at increased risk. Int J Radiat Oncol Biol Phys 51(3):679–690PubMedGoogle Scholar
  13. 13.
    Dignam JJ, Wieand K, Johnson KA, Fisher B, Xu L, Mamounas EP (2003) Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst 95(19):1467–1476PubMedGoogle Scholar
  14. 14.
    Jain M, Miller AB (1997) Tumor characteristics and survival of breast cancer patients in relation to premorbid diet and body size. Breast Cancer Res Treat 42(1):43–55PubMedCrossRefGoogle Scholar
  15. 15.
    Carmichael AR, Bendall S, Lockerbie L, Prescott RJ, Bates T (2004) Does obesity compromise survival in women with breast cancer? Breast 13(2):93–96PubMedCrossRefGoogle Scholar
  16. 16.
    Zhang S, Folsom AR, Sellers TA, Kushi LH, Potter JD (1995) Better breast cancer survival for postmenopausal women who are less overweight and eat less fat. The Iowa Women’s Health Study. Cancer 76(2):275–283PubMedCrossRefGoogle Scholar
  17. 17.
    Zumoff B, Dasgupta I (1983) Relationship between body weight and the incidence of positive axillary nodes at mastectomy for breast cancer. J Surg Oncol 22(4):217–220PubMedCrossRefGoogle Scholar
  18. 18.
    Cui Y, Whiteman MK, Flaws JA, Langenberg P, Tkaczuk KH, Bush TL (2002) Body mass and stage of breast cancer at diagnosis. Int J Cancer 98(2):279–283PubMedCrossRefGoogle Scholar
  19. 19.
    Verreault R, Brisson J, Deschenes L, Naud F (1989) Body weight and prognostic indicators in breast cancer. Modifying effect of estrogen receptors. Am J Epidemiol 129(2):260–268PubMedGoogle Scholar
  20. 20.
    Kumar NB, Cantor A, Allen K, Cox CE (2000) Android obesity at diagnosis and breast carcinoma survival: evaluation of the effects of anthropometric variables at diagnosis, including body composition and body fat distribution and weight gain during life span,and survival from breast carcinoma. Cancer 88(12):2751–2757PubMedCrossRefGoogle Scholar
  21. 21.
    Borugian MJ, Sheps SB, Kim-Sing C, Olivotto IA, Van Patten C, Dunn BP, Coldman AJ, Potter JD, Gallagher RP, Hislop TG (2003) Waist-to-hip ratio and breast cancer mortality. Am J Epidemiol 158(10):963–968PubMedCrossRefGoogle Scholar
  22. 22.
    Marret H, Perrotin F, Bougnoux P, Descamps P, Hubert B, Lefranc T, Le Floch O, Lansac J, Body G (2001) Low body mass index is an independent predictive factor of local recurrence after conservative treatment for breast cancer. Breast Cancer Res Treat 66(1):17–23PubMedCrossRefGoogle Scholar
  23. 23.
    Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, Hartwick W, Hoffman B, Hood N (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20(1):42–51PubMedCrossRefGoogle Scholar
  24. 24.
    La Guardia M, Giammanco M (2001) Breast cancer and obesity. Panminerva Med 43(2):123–133PubMedGoogle Scholar
  25. 25.
    Pierce JP, Faerber S, Wright FA, Newman V, Flatt SW, Kealey S, Rock CL, Hryniuk W, Greenberg ER (1997) Feasibility of a randomized trial of a high-vegetable diet to prevent breast cancer recurrence. Nutr Cancer 28(3):282–288PubMedCrossRefGoogle Scholar
  26. 26.
    Newman VA, Thomson CA, Rock CL, Flatt SW, Kealey S, Bardwell WA, Caan BJ, Pierce JP (2005) Achieving substantial changes in eating behavior among women previously treated for breast cancer–an overview of the intervention. J Am Diet Assoc 105(3):382–391; quiz 488PubMedCrossRefGoogle Scholar
  27. 27.
    Rock CL (2003) Diet and breast cancer: can dietary factors influence survival? J Mammary Gland Biol Neoplasia 8(1):119–132PubMedCrossRefGoogle Scholar
  28. 28.
    Gilmore J (1999) Body mass index and health. Health Rep 11(1):31–43(Eng); 33–47(Fre)Google Scholar
  29. 29.
    Pi-Sunyer FX (2002) The obesity epidemic: pathophysiology and consequences of obesity. Obes Res 10(Suppl 2):97S–104SPubMedCrossRefGoogle Scholar
  30. 30.
    Korzeniowski S, Dyba T, Skolyszewski J (1994) Classical prognostic factors for survival and loco-regional control in breast cancer patients treated with radical mastectomy alone. Acta Oncol 33(7):759–765PubMedCrossRefGoogle Scholar
  31. 31.
    Mirza AN, Mirza NQ, Vlastos G, Singletary SE (2002) Prognostic factors in node-negative breast cancer: a review of studies with sample size more than 200 and follow-up more than 5 years. Ann Surg 235(1):10–26PubMedCrossRefGoogle Scholar
  32. 32.
    Maehle BO, Tretli S, Thorsen T (2004) The associations of obesity, lymph node status and prognosis in breast cancer patients: dependence on estrogen and progesterone receptor status. APMIS 112(6):349–357PubMedCrossRefGoogle Scholar
  33. 33.
    Newman SC, Lees AW, Jenkins HJ (1997) The effect of body mass index and oestrogen receptor level on survival of breast cancer patients. Int J Epidemiol 26(3):484–490PubMedCrossRefGoogle Scholar
  34. 34.
    den Tonkelaar I, de Waard F, Seidell JC, Fracheboud J (1995) Obesity and subcutaneous fat patterning in relation to survival of postmenopausal breast cancer patients participating in the DOM-project. Breast Cancer Res Treat 34(2):129–137CrossRefGoogle Scholar
  35. 35.
    Vittinghoff E, Glidden D, Shiboski S, McCulloch C (2006) Regression methods in biostatistics- linear, logistic, survival and repeated measures models. Stat Methods Med Res 15(5):518 ppGoogle Scholar
  36. 36.
    Therneau TM, Grambsch PM (2000) Modeling survival data: extending the cox model, 1st edn. Springer-VerlagGoogle Scholar
  37. 37.
    MathSoft S-PLUS 2000 (1999) Guide to statistics, vol. 1 & 2. User’s Guide; Programmer’s GuideGoogle Scholar
  38. 38.
    Porter GA, Inglis KM, Wood LA, Veugelers PJ (2006) Effect of obesity on presentation of breast cancer. Ann Surg Oncol 13(3):327–332PubMedCrossRefGoogle Scholar
  39. 39.
    Ariel IM, Greenberg J (1977) Obesity obscuring breast cancer: a case report. J Surg Oncol 9(1):45–47PubMedCrossRefGoogle Scholar
  40. 40.
    Elmore JG, Carney PA, Abraham LA, Barlow WE, Egger JR, Fosse JS, Cutter GR, Hendrick RE, D’Orsi CJ, Paliwal P et al (2004) The association between obesity and screening mammography accuracy. Arch Intern Med 164(10):1140–1147PubMedCrossRefGoogle Scholar
  41. 41.
    Stoll BA (1996) Obesity and breast cancer. Int J Obes Relat Metab Disord 20(5):389–392PubMedGoogle Scholar
  42. 42.
    Madarnas Y, Sawka CA, Franssen E, Bjarnason GA (2001) Are medical oncologists biased in their treatment of the large woman with breast cancer? Breast Cancer Res Treat 66(2):123–133PubMedCrossRefGoogle Scholar
  43. 43.
    Dickman PW, Sloggett A, Hills M, Hakulinen T (2004) Regression models for relative survival. Stat Med 23(1):51–64PubMedCrossRefGoogle Scholar
  44. 44.
    Mueller CB, Jeffries W (1975) Cancer of the breast: its outcome as measured by the rate of dying and causes of death. Ann Surg 182(3):334–341PubMedCrossRefGoogle Scholar
  45. 45.
    Schairer C, Mink PJ, Carroll L, Devesa SS (2004) Probabilities of death from breast cancer and other causes among female breast cancer patients. J Natl Cancer Inst 96(17):1311–1321PubMedCrossRefGoogle Scholar
  46. 46.
    Enger SM, Greif JM, Polikoff J, Press M (2004) Body weight correlates with mortality in early-stage breast cancer. Arch Surg 139(9):954–958; discussion 958–960PubMedCrossRefGoogle Scholar
  47. 47.
    Boyd NF, Campbell JE, Germanson T, Thomson DB, Sutherland DJ, Meakin JW (1981) Body weight and prognosis in breast cancer. J Natl Cancer Inst 67(4):785–789PubMedGoogle Scholar
  48. 48.
    Hebert JR, Augustine A, Barone J, Kabat GC, Kinne DW, Wynder EL (1988) Weight, height and body mass index in the prognosis of breast cancer: early results of a prospective study. Int J Cancer 42(3):315–318PubMedCrossRefGoogle Scholar
  49. 49.
    Senie RT, Rosen PP, Rhodes P, Lesser ML, Kinne DW (1992) Obesity at diagnosis of breast carcinoma influences duration of disease-free survival. Ann Intern Med 116(1):26–32PubMedGoogle Scholar
  50. 50.
    McNee RK, Mason BH, Neave LM, Kay RG (1987) Influence of height, weight, and obesity on breast cancer incidence and recurrence in Auckland, New Zealand. Breast Cancer Res Treat 9(2):145–150PubMedCrossRefGoogle Scholar
  51. 51.
    Bianchini F, Kaaks R, Vainio H (2002) Overweight, obesity, and cancer risk. Lancet Oncol 3(9):565–574PubMedCrossRefGoogle Scholar
  52. 52.
    Maehle BO, Tretli S (1996) Pre-morbid body-mass-index in breast cancer: reversed effect on survival in hormone receptor negative patients. Breast Cancer Res Treat 41(2):123–130PubMedCrossRefGoogle Scholar
  53. 53.
    Louis-Sylvestre C, Clough K, Asselain B, Vilcoq JR, Salmon RJ, Campana F, Fourquet A (2004) Axillary treatment in conservative management of operable breast cancer: dissection or radiotherapy? Results of a randomized study with 15 years of follow-up. J Clin Oncol 22(1):97–101PubMedCrossRefGoogle Scholar
  54. 54.
    Greco M, Agresti R, Cascinelli N, Casalini P, Giovanazzi R, Maucione A, Tomasic G, Ferraris C, Ammatuna M, Pilotti S et al (2000) Breast cancer patients treated without axillary surgery: clinical implications and biologic analysis. Ann Surg 232(1):1–7PubMedCrossRefGoogle Scholar
  55. 55.
    Zurrida S, Orecchia R, Galimberti V, Luini A, Giannetti I, Ballardini B, Amadori A, Veronesi G, Veronesi U (2002) Axillary radiotherapy instead of axillary dissection: a randomized trial. Italian Oncological Senology Group. Ann Surg Oncol 9(2):156–160PubMedCrossRefGoogle Scholar
  56. 56.
    Martelli G, Boracchi P, De Palo M, Pilotti S, Oriana S, Zucali R, Daidone MG, De Palo G (2005) A randomized trial comparing axillary dissection to no axillary dissection in older patients with T1N0 breast cancer: results after 5 years of follow-up. Ann Surg 242(1):1–6; discussion 7–9PubMedCrossRefGoogle Scholar
  57. 57.
    Veronesi U, Orecchia R, Zurrida S, Galimberti V, Luini A, Veronesi P, Gatti G, D’Aiuto G, Cataliotti L, Paolucci R et al (2005) Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy. Ann Oncol 16(3):383–388PubMedCrossRefGoogle Scholar
  58. 58.
    Hoebers FJ, Borger JH, Hart AA, Peterse JL, Th EJ, Lebesque JV (2000) Primary axillary radiotherapy as axillary treatment in breast-conserving therapy for patients with breast carcinoma and clinically negative axillary lymph nodes. Cancer 88(7):1633–1642PubMedCrossRefGoogle Scholar
  59. 59.
    Garrow JS, Webster J (1985) Quetelet’s index (W/H2) as a measure of fatness. Int J Obes 9(2):147–153PubMedGoogle Scholar
  60. 60.
    Wellens RI, Roche AF, Khamis HJ, Jackson AS, Pollock ML, Siervogel RM (1996) Relationships between the body mass index and body composition. Obes Res 4(1):35–44PubMedGoogle Scholar
  61. 61.
    Frankenfield DC, Rowe WA, Cooney RN, Smith JS, Becker D (2001) Limits of body mass index to detect obesity and predict body composition. Nutrition 17(1):26–30PubMedCrossRefGoogle Scholar
  62. 62.
    Kyogoku S, Hirohata T, Takeshita S, Nomura Y, Shigematsu T, Horie A (1990) Survival of breast-cancer patients and body size indicators. Int J Cancer 46(5):824–831PubMedCrossRefGoogle Scholar
  63. 63.
    Himes JH, Bouchard C, Pheley AM (1991) Lack of correspondence among measures identifying the obese. Am J Prev Med 7(2):107–111PubMedGoogle Scholar
  64. 64.
    Suissa S, Pollak M, Spitzer WO, Margolese R (1989) Body size and breast cancer prognosis: a statistical explanation of the discrepancies. Cancer Res 49(11):3113–3116PubMedGoogle Scholar
  65. 65.
    Bastarrachea J, Hortobagyi GN, Smith TL, Kau SW, Buzdar AU (1994) Obesity as an adverse prognostic factor for patients receiving adjuvant chemotherapy for breast cancer. Ann Intern Med 120(1):18–25PubMedGoogle Scholar
  66. 66.
    Demark-Wahnefried W, Peterson BL, Winer EP, Marks L, Aziz N, Marcom PK, Blackwell K, Rimer BK (2001) Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 19(9):2381–2389PubMedGoogle Scholar
  67. 67.
    Goodwin PJ, Ennis M, Pritchard KI, McCready D, Koo J, Sidlofsky S, Trudeau M, Hood N, Redwood S (1999) Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis. J Clin Oncol 17(1):120–129PubMedGoogle Scholar
  68. 68.
    Kumar NB, Allen K, Cantor A, Cox CE, Greenberg H, Shah S, Lyman GH (1997) Weight gain associated with adjuvant tamoxifen therapy in stage I and II breast cancer: fact or artifact? Breast Cancer Res Treat 44(2):135–143PubMedCrossRefGoogle Scholar
  69. 69.
    Rock CL, Flatt SW, Newman V, Caan BJ, Haan MN, Stefanick ML, Faerber S, Pierce JP (1999) Factors associated with weight gain in women after diagnosis of breast cancer. Women’s Healthy Eating and Living Study Group. J Am Diet Assoc 99(10):1212–1221PubMedCrossRefGoogle Scholar
  70. 70.
    Guthrie JR, Dennerstein L, Dudley EC (1999) Weight gain and the menopause: a 5-year prospective study. Climacteric 2(3):205–211PubMedCrossRefGoogle Scholar
  71. 71.
    Stoll BA (1999) Perimenopausal weight gain and progression of breast cancer precursors. Cancer Detect Prev 23(1):31–36PubMedCrossRefGoogle Scholar
  72. 72.
    Charles MA, Basdevant A, Eschwege E (2002) Prevalence of obesity in adults in France: the situation in 2000 established from the OBEPI Study. Ann Endocrinol (Paris) 63(2 Pt 1):154–158Google Scholar
  73. 73.
    Goodwin PJ, Panzarella T, Boyd NF (1988) Weight gain in women with localized breast cancer—a descriptive study. Breast Cancer Res Treat 11(1):59–66PubMedCrossRefGoogle Scholar
  74. 74.
    Caan BJ, Emond JA, Natarajan L, Castillo A, Gunderson EP, Habel L, Jones L, Newman VA, Rock CL, Slattery ML et al (2006) Post-diagnosis weight gain and breast cancer recurrence in women with early stage breast cancer. Breast Cancer Res Treat 99:47–57PubMedCrossRefGoogle Scholar
  75. 75.
    Kroenke CH, Chen WY, Rosner B, Holmes MD (2005) Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol 23(7):1370–1378PubMedCrossRefGoogle Scholar
  76. 76.
    Benson JR, Weaver DL, Mittra I, Hayashi M (2003) The TNM staging system and breast cancer. Lancet Oncol 4(1):56–60PubMedCrossRefGoogle Scholar
  77. 77.
    Montero S, Guzman C, Vargas C, Ballestin C, Cortes-Funes H, Colomer R (2001) Prognostic value of cytosolic p53 protein in breast cancer. Tumour Biol 22(5):337–344PubMedCrossRefGoogle Scholar
  78. 78.
    Railo M, Lundin J, Haglund C, von Smitten K, von Boguslawsky K, Nordling S (1997) Ki-67, p53, Er-receptors, ploidy and S-phase as prognostic factors in T1 node negative breast cancer. Acta Oncol 36(4):369–374PubMedCrossRefGoogle Scholar
  79. 79.
    Joensuu H, Lehtimaki T, Holli K, Elomaa L, Turpeenniemi-Hujanen T, Kataja V, Anttila A, Lundin M, Isola J, Lundin J (2004) Risk for distant recurrence of breast cancer detected by mammography screening or other methods. JAMA 292(9):1064–1073PubMedCrossRefGoogle Scholar
  80. 80.
    Gordon NH, Crowe JP, Brumberg DJ, Berger NA (1992) Socioeconomic factors and race in breast cancer recurrence and survival. Am J Epidemiol 135(6):609–618PubMedGoogle Scholar
  81. 81.
    Stoll BA (1996) Obesity, social class and Western diet: a link to breast cancer prognosis. Eur J Cancer 32A(8):1293–1295PubMedCrossRefGoogle Scholar
  82. 82.
    Hilsenbeck SG, Ravdin PM, de Moor CA, Chamness GC, Osborne CK, Clark GM (1998) Time-dependence of hazard ratios for prognostic factors in primary breast cancer. Breast Cancer Res Treat 52(1–3):227–237PubMedCrossRefGoogle Scholar
  83. 83.
    Glidden DV, Vittinghoff E (2004) Modelling clustered survival data from multicentre clinical trials. Stat Med 23(3):369–388PubMedCrossRefGoogle Scholar
  84. 84.
    Commenges D (1999) Competitive risks and multi-state models in epidemiology. Rev Epidemiol Sante Publique 47(6):605–611PubMedGoogle Scholar
  85. 85.
    Hougaard P (2000) Analysis of multivariate survival data. Springer, New YorkGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • Bilal Majed
    • 1
    • 2
  • Thierry Moreau
    • 3
  • Kamel Senouci
    • 4
  • Rémi J. Salmon
    • 5
  • Alain Fourquet
    • 5
  • Bernard Asselain
    • 1
  1. 1.Biostatistics DepartmentCurie InstituteParisFrance
  2. 2.ArrasFrance
  3. 3.INSERM UNIT 780: Epidemiology and Biostatistics, Paul-Brousse HospitalVillejuif CedexFrance
  4. 4.WHOLyonFrance
  5. 5.Breast Cancer GroupCurie Institute ParisFrance

Personalised recommendations