Breast Cancer Research and Treatment

, Volume 134, Issue 2, pp 769–781 | Cite as

Body size and breast cancer prognosis in relation to hormone receptor and menopausal status: a meta-analysis

  • Saroj Niraula
  • Alberto Ocana
  • Marguerite Ennis
  • Pamela J. GoodwinEmail author


Obesity is associated with poor survival after breast cancer diagnosis in individual studies and meta-analyses. Evidence regarding associations of obesity with breast cancer-specific survival (BCSS) and overall survival (OS) in relation to hormone receptor status, or BCSS in relation to menopausal status has not been evaluated in a previous meta-analysis. In this study, we conducted a meta-analysis of the association of obesity with OS and BCSS in relation to hormone receptor status and menopausal status. MEDLINE, EMBASE, and COCHRANE databases from the first record to December 2011 and presentations made at major international meetings in the last 5 years were searched. We included observational or interventional studies reporting hazard ratios (HRs) of obesity with OS and/or BCSS in relation to hormone receptor and/or menopausal status. Twenty-one studies qualified, meeting the above criteria. The pooled HR for OS in heavier versus lighter women was 1.31 (95 % CI 1.17–1.46) for estrogen receptor/progesterone receptor (ER/PgR) positive cancers; 1.18 (95 % CI 1.06–1.31) for ER/PgR negative cancers; and the difference between the two groups was not significant (p = 0.31). The pooled HR for OS in heavier versus lighter women was 1.23 (95 % CI 1.07–1.42) for premenopausal women and 1.15 (95 % CI 1.06–1.26) for post-menopausal women, and the difference between the two groups was not significant (p = 0.57). Comparable pooled HRs for BCSS were 1.36 (95 % CI 1.20–1.54) for ER/PgR positive cancers and 1.46 (95 % CI 0.98–2.19) for ER/PgR negative cancers; and 1.18 (95 % CI 0.82–1.70) for pre-menopausal women and 1.38 (95 % CI 1.11–1.71) for post-menopausal women, also without significant group differences. Results were similar after adjustment for BMI measurement technique, years of follow-up, or study design. These findings led us to conclude that there is no evidence showing that the association of obesity with breast cancer outcome differs by hormone receptor or menopausal status. This has implications for studies of weight loss interventions in the adjuvant BC setting.


Obesity Body mass index BMI Breast cancer Prognosis Survival Hormone receptor ER Menopausal 



We would like to thank Drs. Prakesh Shah and Joseph Beyene at University of Toronto for their valuable suggestions during preparation of this manuscript.

Conflict of interest

This is to confirm that none of the authors of the above manuscript have conflict of interest of any kind which may arise from being named as an author on the manuscript.

It is to certify that (i) all financial support or benefits received by me, by any member of my immediate family, or any individual or entity with whom or with which I have a significant relationship from any commercial source related directly or indirectly to the scientific work reported in the article have been disclosed and have been included in the submitted manuscript, (II) neither I, nor any member of my immediate family, nor any individual or entity with whom or with which I have a significant relationship has a financial interest in the subject matter discussed in the manuscript, except as disclosed (I understand an example of such a financial interest would be a stock interest in any business entity which is included in the subject matter of the manuscript or which sells a product relating to the subject matter of the manuscript.), (III) all funding sources supporting the work and all institutional or corporate affiliations are acknowledged in a footnote, and (Iv) I have had full access to all the data in the study (if applicable) and thereby accept full responsibility for the integrity of the data and the accuracy of the data analysis.

Signed by: Saroj Niraula, Alberto Ocana, Marguerite Ennis and Pamela J. Goodwin


  1. 1.
    Kelly T et al (2008) Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond) 32(9):1431–1437CrossRefGoogle Scholar
  2. 2.
    Renehan AG et al (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578PubMedCrossRefGoogle Scholar
  3. 3.
    van den Brandt PA et al (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152(6):514–527PubMedCrossRefGoogle Scholar
  4. 4.
    Harvie M, Hooper L, Howell AH (2003) Central obesity and breast cancer risk: a systematic review. Obes Rev 4(3):157–173PubMedCrossRefGoogle Scholar
  5. 5.
    Goodwin P et al (1995) Development of a weight management program in women with newly diagnosed locoregional breast cancer. In: 11th international congress of psychosomatic obstetrics and gynaecology, Basel, SwitzerlandGoogle Scholar
  6. 6.
    Protani M, Coory M, Martin JH (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123(3):627–635PubMedCrossRefGoogle Scholar
  7. 7.
    Ryu S et al (2001) Is body mass index the prognostic factor in breast cancer?: a meta-analysis. J Korean Med Sci 16(5):610–614PubMedGoogle Scholar
  8. 8.
    Hursting SD et al (2008) Reducing the weight of cancer: mechanistic targets for breaking the obesity-carcinogenesis link. Best Pract Res Clin Endocrinol Metab 22(4):659–669PubMedCrossRefGoogle Scholar
  9. 9.
    Renehan AG, Roberts DL, Dive C (2008) Obesity and cancer: pathophysiological and biological mechanisms. Arch Physiol Biochem 114(1):71–83PubMedCrossRefGoogle Scholar
  10. 10.
    Subbaramaiah K et al (2011) Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res (Phila) 4(3):329–346CrossRefGoogle Scholar
  11. 11.
    Morris PG et al (2011) Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res (Phila) 4(7):1021–1029CrossRefGoogle Scholar
  12. 12.
    Pfeiler G et al (2011) Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. J Clin Oncol 29(19):2653–2659PubMedCrossRefGoogle Scholar
  13. 13.
    Bowers L et al. (2010) Obesity promotes breast cancer progression and tamoxifen resistance via cross-talk between growth factor and estrogen signaling pathways. In: San Antonio breast cancer symposium 2010 [PD09-06]Google Scholar
  14. 14.
    Wells G et al (2011) The Newcastle–Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. Assessed on January 20, 2011
  15. 15.
    Deeks J, Higgins J, Altman D (2006) Analysing and presenting results: cochrane handbook for systematic reviews of interventions 4 2 5. In: The cochrane library. John Wiley and Sons, ChichesterGoogle Scholar
  16. 16.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188PubMedCrossRefGoogle Scholar
  17. 17.
    Higgins JP et al (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560PubMedCrossRefGoogle Scholar
  18. 18.
    van Houwelingen HC, Arends LR, Stijnen T (2002) Advanced methods in meta-analysis: multivariate approach and meta-regression. Stat Med 21(4):589–624PubMedCrossRefGoogle Scholar
  19. 19.
    Viechtbauer W (2010) Conducting meta-analyses in R with the metafor package. J Stat Softw 36(3):1–48Google Scholar
  20. 20.
    de Azambuja E et al (2010) The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02-98 trial. Breast Cancer Res Treat 119(1):145–153PubMedCrossRefGoogle Scholar
  21. 21.
    Berclaz G et al (2004) Body mass index as a prognostic feature in operable breast cancer: the International Breast Cancer Study Group experience. Ann Oncol 15(6):875–884PubMedCrossRefGoogle Scholar
  22. 22.
    Conroy SM et al (2011) Obesity and breast cancer survival in ethnically diverse postmenopausal women: the Multiethnic Cohort Study. Breast Cancer Res Treat 129(2):565–574PubMedCrossRefGoogle Scholar
  23. 23.
    Chang S et al (2000) Inflammatory breast cancer survival: the role of obesity and menopausal status at diagnosis. Breast Cancer Res Treat 64(2):157–163PubMedCrossRefGoogle Scholar
  24. 24.
    Chen X et al (2010) Obesity and weight change in relation to breast cancer survival. Breast Cancer Res Treat 122(3):823–833PubMedCrossRefGoogle Scholar
  25. 25.
    Dal Maso L et al (2008) Effect of obesity and other lifestyle factors on mortality in women with breast cancer. Int J Cancer 123(9):2188–2194PubMedCrossRefGoogle Scholar
  26. 26.
    Dignam JJ et al (2003) Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst 95(19):1467–1476PubMedCrossRefGoogle Scholar
  27. 27.
    Dignam JJ et al (2006) Effects of obesity and race on prognosis in lymph node-negative, estrogen receptor-negative breast cancer. Breast Cancer Res Treat 97(3):245–254PubMedCrossRefGoogle Scholar
  28. 28.
    Daling JR et al (2001) Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma. Cancer 92(4):720–729PubMedCrossRefGoogle Scholar
  29. 29.
    Enger SM, Bernstein L (2004) Exercise activity, body size and premenopausal breast cancer survival. Br J Cancer 90(11):2138–2141PubMedGoogle Scholar
  30. 30.
    Goodwin PJ et al (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20(1):42–51PubMedCrossRefGoogle Scholar
  31. 31.
    Keegan THM et al (2010) Past recreational physical activity, body size, and all-cause mortality following breast cancer diagnosis: results from the Breast Cancer Family Registry. Breast Cancer Res Treat 123(2):531–542PubMedCrossRefGoogle Scholar
  32. 32.
    Kwan ML et al. (2011) Pre-diagnosis body mass index and survival after breast cancer in the After Breast Cancer Pooling Project. Breast Cancer Research & TreatmentGoogle Scholar
  33. 33.
    Loi S et al (2005) Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 14(7):1686–1691PubMedCrossRefGoogle Scholar
  34. 34.
    Majed B et al (2008) Is obesity an independent prognosis factor in woman breast cancer? Breast Cancer Res Treat 111(2):329–342PubMedCrossRefGoogle Scholar
  35. 35.
    Vitolins MZ, Kimmick GG, Case LD (2008) BMI influences prognosis following surgery and adjuvant chemotherapy for lymph node positive breast cancer. Breast J 14(4):357–365PubMedCrossRefGoogle Scholar
  36. 36.
    Whiteman MK et al (2005) Body mass and mortality after breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev 14(8):2009–2014PubMedCrossRefGoogle Scholar
  37. 37.
    Sparano JA et al (2008) Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 358(16):1663–1671PubMedCrossRefGoogle Scholar
  38. 38.
    Davidson NE et al (2005) Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol 23(25):5973–5982PubMedCrossRefGoogle Scholar
  39. 39.
    Fetting JH et al (1998) Sixteen-week multidrug regimen versus cyclophosphamide, doxorubicin, and fluorouracil as adjuvant therapy for node-positive, receptor-negative breast cancer: an Intergroup study. J Clin Oncol 16(7):2382–2391PubMedGoogle Scholar
  40. 40.
    Sparano J et al. (2010) Obesity at diagnosis is associated with inferior outcomes in hormone receptor positive breast cancer. In: San Antonio breast cancer symphosium 2010 [S2-1]Google Scholar
  41. 41.
    Sestak I et al (2010) Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: an exploratory analysis from the ATAC trial. J Clin Oncol 28(21):3411–3415PubMedCrossRefGoogle Scholar
  42. 42.
    den Tonkelaar I, Seidell JC, Collette HJ (1995) Body fat distribution in relation to breast cancer in women participating in the DOM-project. Breast Cancer Res Treat 34(1):55–61CrossRefGoogle Scholar
  43. 43.
    Demirkan B, Alacacioglu A, Yilmaz U (2007) Relation of body mass index (BMI) to disease free (DFS) and distant disease free survivals (DDFS) among Turkish women with operable breast carcinoma. Jpn J Clin Oncol 37(4):256–265PubMedCrossRefGoogle Scholar
  44. 44.
    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
  45. 45.
    Mohle-Boetani JC et al (1988) Body size, reproductive factors, and breast cancer survival. Prev Med 17(5):634–642PubMedCrossRefGoogle Scholar
  46. 46.
    Lu Y et al (2011) Obesity and survival among black women and white women 35 to 64 years of age at diagnosis with invasive breast cancer. J Clin Oncol 29(25):3358–3365PubMedCrossRefGoogle Scholar
  47. 47.
    Jain MG et al (2005) Body mass index and mortality in women: follow-up of the Canadian National Breast Screening Study cohort. Int J Obes 29(7):792–797CrossRefGoogle Scholar
  48. 48.
    Kroenke CH et al (2005) Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol 23(7):1370–1378PubMedCrossRefGoogle Scholar
  49. 49.
    den Tonkelaar I et al (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
  50. 50.
    Abrahamson PE et al (2006) General and abdominal obesity and survival among young women with breast cancer. Cancer Epidemiol Biomarkers Prev 15(10):1871–1877PubMedCrossRefGoogle Scholar
  51. 51.
    Barnett GC et al (2008) Risk factors for the incidence of breast cancer: do they affect survival from the disease? J Clin Oncol 26(20):3310–3316PubMedCrossRefGoogle Scholar
  52. 52.
    Bastarrachea J et al (1994) Obesity as an adverse prognostic factor for patients receiving adjuvant chemotherapy for breast cancer. Ann Intern Med 120(1):18–25PubMedGoogle Scholar
  53. 53.
    Borugian MJ et al (2003) Waist-to-hip ratio and breast cancer mortality. Am J Epidemiol 158(10):963–968PubMedCrossRefGoogle Scholar
  54. 54.
    Caan BJ et al (2008) Pre-diagnosis body mass index, post-diagnosis weight change, and prognosis among women with early stage breast cancer. Cancer Causes Control 19(10):1319–1328PubMedCrossRefGoogle Scholar
  55. 55.
    Carmichael AR et al (2004) Does obesity compromise survival in women with breast cancer? Breast 13(2):93–96PubMedCrossRefGoogle Scholar
  56. 56.
    Cleveland RJ et al (2007) Weight gain prior to diagnosis and survival from breast cancer. Cancer Epidemiol Biomarkers Prev 16(9):1803–1811PubMedCrossRefGoogle Scholar
  57. 57.
    Dawood S et al (2008) Prognostic value of body mass index in locally advanced breast cancer. Clin Cancer Res 14(6):1718–1725PubMedCrossRefGoogle Scholar
  58. 58.
    Eley JW et al (1994) Racial differences in survival from breast cancer. Results of the National Cancer Institute Black/White Cancer Survival Study. JAMA 272(12):947–954PubMedCrossRefGoogle Scholar
  59. 59.
    Greenberg ER et al (1985) Body size and survival in premenopausal breast cancer. Br J Cancer 51(5):691–697PubMedCrossRefGoogle Scholar
  60. 60.
    Hebert JR, Hurley TG, Ma Y (1998) The effect of dietary exposures on recurrence and mortality in early stage breast cancer. Breast Cancer Res Treat 51(1):17–28PubMedCrossRefGoogle Scholar
  61. 61.
    Holmberg L et al (1994) Oral contraceptives and prognosis in breast cancer: effects of duration, latency, recency, age at first use and relation to parity and body mass index in young women with breast cancer. Eur J Cancer 30A(3):351–354PubMedCrossRefGoogle Scholar
  62. 62.
    Katoh A, Watzlaf VJ, D’Amico F (1994) An examination of obesity and breast cancer survival in post-menopausal women. Br J Cancer 70(5):928–933PubMedCrossRefGoogle Scholar
  63. 63.
    Labidi SI et al (2008) Inflammatory breast cancer in Tunisia in the era of multimodality therapy. Ann Oncol 19(3):473–480PubMedCrossRefGoogle Scholar
  64. 64.
    Litton JK et al (2008) Relationship between obesity and pathologic response to neoadjuvant chemotherapy among women with operable breast cancer. J Clin Oncol 26(25):4072–4077PubMedCrossRefGoogle Scholar
  65. 65.
    Mason BH et al (1990) Season of tumour detection influences factors predicting survival of patients with breast cancer. Breast Cancer Res Treat 15(1):27–37PubMedCrossRefGoogle Scholar
  66. 66.
    Moon HG, Han W, Noh DY (2009) Underweight and breast cancer recurrence and death: a report from the Korean Breast Cancer Society. J Clin Oncol 27(35):5899–5905PubMedCrossRefGoogle Scholar
  67. 67.
    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
  68. 68.
    Nichols HB et al (2009) Body mass index before and after breast cancer diagnosis: associations with all-cause, breast cancer, and cardiovascular disease mortality. Cancer Epidemiol Biomarkers Prev 18(5):1403–1409PubMedCrossRefGoogle Scholar
  69. 69.
    Petrelli JM et al (2002) Body mass index, height, and postmenopausal breast cancer mortality in a prospective cohort of US women. Cancer Causes Control 13(4):325–332PubMedCrossRefGoogle Scholar
  70. 70.
    Pierce JP et al (2007) Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. J Clin Oncol 25(17):2345–2351PubMedCrossRefGoogle Scholar
  71. 71.
    Reeves GK et al (2000) Hormonal and other factors in relation to survival among breast cancer patients. Int J Cancer 89(3):293–299PubMedCrossRefGoogle Scholar
  72. 72.
    Rosenberg L, Czene K, Hall P (2009) Obesity and poor breast cancer prognosis: an illusion because of hormone replacement therapy? Br J Cancer 100(9):1486–1491PubMedCrossRefGoogle Scholar
  73. 73.
    Saxe GA et al (1999) Diet and risk for breast cancer recurrence and survival. Breast Cancer Res Treat 53(3):241–253PubMedCrossRefGoogle Scholar
  74. 74.
    Tao MH et al (2006) Association of overweight with breast cancer survival. Am J Epidemiol 163(2):101–107PubMedCrossRefGoogle Scholar
  75. 75.
    Vatten LJ, Foss OP, Kvinnsland S (1991) Overall survival of breast cancer patients in relation to preclinically determined total serum cholesterol, body mass index, height and cigarette smoking: a population-based study. Eur J Cancer 27(5):641–646PubMedCrossRefGoogle Scholar
  76. 76.
    Chlebowski RT et al (2006) Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women’s Intervention Nutrition Study. J Natl Cancer Inst 98(24):1767–1776PubMedCrossRefGoogle Scholar
  77. 77.
    Rock CL et al (2008) Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer. Cancer Epidemiol Biomark Prev 17(3):614–620CrossRefGoogle Scholar
  78. 78.
    Mulligan AM et al (2007) Insulin receptor is an independent predictor of a favorable outcome in early stage breast cancer. Breast Cancer Res Treat 106(1):39–47PubMedCrossRefGoogle Scholar
  79. 79.
    Law JH et al (2008) Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related to poor survival. Cancer Res 68(24):10238–10246PubMedCrossRefGoogle Scholar
  80. 80.
    Goodwin PJ et al (2005) Is leptin a mediator of adverse prognostic effects of obesity in breast cancer? J Clin Oncol 23(25):6037–6042PubMedCrossRefGoogle Scholar
  81. 81.
    Duggan C et al (2011) Associations of insulin resistance and adiponectin with mortality in women with breast cancer. J Clin Oncol 29(1):32–39PubMedCrossRefGoogle Scholar
  82. 82.
    Emaus A et al (2010) Metabolic profile, physical activity, and mortality in breast cancer patients. Breast Cancer Res Treat 121(3):651–660PubMedCrossRefGoogle Scholar
  83. 83.
    Erickson K et al (2011) Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast cancer. J Clin Oncol 29(1):54–60PubMedCrossRefGoogle Scholar
  84. 84.
    Irwin ML et al (2011) Fasting C-peptide levels and death resulting from all causes and breast cancer: the health, eating, activity, and lifestyle study. J Clin Oncol 29(1):47–53PubMedCrossRefGoogle Scholar
  85. 85.
    Ma J et al (2008) Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis. Lancet Oncol 9(11):1039–1047PubMedCrossRefGoogle Scholar
  86. 86.
    Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8(12):915–928PubMedCrossRefGoogle Scholar
  87. 87.
    Doyle SL et al (2011) Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proc Nutr Soc 1–9Google Scholar
  88. 88.
    Goodwin PJ et al (2011) Insulin- and obesity-related variables in early-stage breast cancer: correlations and time course of prognostic associations. J Clin OncolGoogle Scholar
  89. 89.
    Egger M, Schneider M, Davey Smith G (1998) Spurious precision? Meta-analysis of observational studies. BMJ 316(7125):140–144PubMedCrossRefGoogle Scholar
  90. 90.
    Thivat E et al (2010) Weight change during chemotherapy changes the prognosis in non metastatic breast cancer for the worse. BMC Cancer 10:648PubMedCrossRefGoogle Scholar
  91. 91.
    Chauvet B et al (1990) Prognostic significance of breast relapse after conservative treatment in node-negative early breast cancer. Int J Radiat Oncol Biol Phys 19(5):1125–1130PubMedCrossRefGoogle Scholar
  92. 92.
    Marret H et al (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

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Saroj Niraula
    • 1
  • Alberto Ocana
    • 1
  • Marguerite Ennis
    • 2
  • Pamela J. Goodwin
    • 1
    • 3
    Email author
  1. 1.Mount Sinai Hospital and Princess Margaret HospitalTorontoCanada
  2. 2.MarkhamCanada
  3. 3.Division of Clinical Epidemiology, Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity of TorontoTorontoCanada

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