Clinical Studies Examining the Impact of Obesity on Breast Cancer Risk and Prognosis

  • Rishi Jain
  • Howard D. Strickler
  • Eugene Fine
  • Joseph A. Sparano


Obesity is associated with an increased risk of breast cancer, and increased risk of recurrence in women who develop breast cancer. Evidence suggests that the risk of estrogen-receptor (ER)-positive breast cancer is increased in obese postmenopausal women, whereas in premenopausal women the risk of triple negative breast cancer is increased. Nonetheless, the presence of obesity at diagnosis, and possibly weight gain after diagnosis, may independently contribute to an individual’s risk of recurrence of both pre- and postmenopausal breast cancer. Factors associated with adiposity that are likely contributing factors include hyperinsulinemia, inflammation, and relative hyperestrogenemia. Some studies suggest that some aromatase inhibitors may be less effective in obese women than lean women. Clinical trials have evaluated pharmacologic (eg, metformin) and dietary/lifestyle interventions to reduce breast cancer recurrence, although these interventions have not been tested in obese women who may be most likely to benefit from them. Further research is required in order to identify adiposity-associated factors driving recurrence, and design clinical trials to specifically test interventions in obese women at highest risk of recurrence.


Obesity Breast cancer Body mass index Prognosis Recurrence 



breast cancer specific survival


body mass index


confidence interval


disease free survival


estrogen receptor


fluorodeoxyglucose positron emission


human epidermal growth factor receptor 2


homeostasis model assessment


hazard ratio


insulin-like growth factor


low carbohydrate


mammalian target of rapamycin


odds ratio


overall survival


phosphoinositide 3-kinase


relapse free survival


  1. 1.
    Calle EE, Rodriguez C, Walker-Thurmond K, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625–38.PubMedCrossRefGoogle Scholar
  2. 2.
    Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4:579–91.PubMedCrossRefGoogle Scholar
  3. 3.
    Flegal KM, Carroll MD, Ogden CL, et al. Prevalence and trends in obesity among US adults, 1999–2008. JAMA. 2010;303:235–41.PubMedCrossRefGoogle Scholar
  4. 4.
    Ogden CL, Carroll MD, Kit BK, et al. Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief. 2012:1–8.Google Scholar
  5. 5.
    Schmitz KH, Neuhouser ML, Agurs-Collins T, et al. Impact of obesity on cancer survivorship and the potential relevance of race and ethnicity. J Natl Cancer Inst. 2013;105:1344–54.PubMedCrossRefGoogle Scholar
  6. 6.
    Flegal KM, Kit BK, Orpana H, et al. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309:71–82.PubMedCrossRefGoogle Scholar
  7. 7.
    Pollack A. A.M.A. Recognizes Obesity as a Disease. New York times, June 18. 2013.Google Scholar
  8. 8.
    Cheraghi Z, Poorolajal J, Hashem T, et al. Effect of body mass index on breast cancer during premenopausal and postmenopausal periods: a meta-analysis. PLoS One. 2012;7:e51446.Google Scholar
  9. 9.
    Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371:569–78.PubMedCrossRefGoogle Scholar
  10. 10.
    Protani M, Coory M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat. 2010;123:627–35.PubMedCrossRefGoogle Scholar
  11. 11.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.PubMedCrossRefGoogle Scholar
  12. 12.
    Gunter MJ, Hoover DR, Yu H, et al. Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2009;101:48–60.PubMedCrossRefGoogle Scholar
  13. 13.
    Huang Z, Hankinson SE, Colditz GA, et al. Dual effects of weight and weight gain on breast cancer risk [see comments]. JAMA. 1997;278:1407–11.PubMedCrossRefGoogle Scholar
  14. 14.
    Kerlikowske K, Walker R, Miglioretti DL, et al. Obesity, mammography use and accuracy, and advanced breast cancer risk. J Natl Cancer Inst. 2008;100:1724–33.PubMedCrossRefGoogle Scholar
  15. 15.
    Li CI, Malone KE, Daling JR. Interactions between body mass index and hormone therapy and postmenopausal breast cancer risk (United States). Cancer Causes Control. 2006;17:695–703.PubMedCrossRefGoogle Scholar
  16. 16.
    Suzuki R, Iwasaki M, Inoue M, et al. Body weight at age 20 years, subsequent weight change and breast cancer risk defined by estrogen and progesterone receptor status–the Japan public health center-based prospective study. Int J Cancer. 2011;129:1214–24.Google Scholar
  17. 17.
    Pierobon MFC. Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2013;137:307–14.PubMedCrossRefGoogle Scholar
  18. 18.
    Protani M, Coory M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat. 2010;123:627–35Google Scholar
  19. 19.
    Kamineni A, Anderson ML, White E, et al. Body mass index, tumor characteristics, and prognosis following diagnosis of early-stage breast cancer in a mammographically screened population. Cancer Causes Control. 2013;24:305–12.Google Scholar
  20. 20.
    Schmitz KH, Neuhouser ML, Agurs-Collins T, et al. Impact of obesity on cancer survivorship and the potential relevance of race and ethnicity. J Natl Cancer Inst. 2013.Google Scholar
  21. 21.
    Griggs JJSM, Lyman GH. Undertreatment of obese women receiving breast cancer chemotherapy. Arch Intern Med. 2005;165:1267–73.PubMedCrossRefGoogle Scholar
  22. 22.
    Rosner GL, Hargis JB, Hollis DR, et al. Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from cancer and leukemia group B study 8541. J Clin Oncol. 1996;14:3000–8.PubMedGoogle Scholar
  23. 23.
    Goodwin PJ, Ennis M, Pritchard KI, et al. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol. 2002;20:42–51.PubMedCrossRefGoogle Scholar
  24. 24.
    Goodwin PJ, Ennis M, Pritchard KI, et al. Insulin-like growth factor binding proteins 1 and 3 and breast cancer outcomes. Breast Cancer Res Treat. 2002;74:65–76.PubMedCrossRefGoogle Scholar
  25. 25.
    Subbaramaiah K, Morris PG, Zhou XK, et al. Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. Cancer Discov. 2012;2:356–65.PubMedCrossRefGoogle Scholar
  26. 26.
    Folkerd EJ, Dixon JM, Renshaw L, et al. Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer. J Clin Oncol. 2012;30:2977–80.PubMedCrossRefGoogle Scholar
  27. 27.
    Majed BMT, Senouci K, et al. Is obesity an independent prognosis factor in women breast cancer. Breast Cancer Res Treat. 2008;111:329–42.PubMedCrossRefGoogle Scholar
  28. 28.
    Sparano JAWM, Zhar F, et al. Obesity at diagnosis is associated with inferior outcomes in hormone receptor-positive operable breast cancer. Cancer. 2012;118:5937–46.PubMedCrossRefGoogle Scholar
  29. 29.
    Ligibel JACC, Liu MC, et al. Body mass index (BMI), tumor subtype, and relapse-free survival (RFS) in CALGB 9741 (Aliance). J Clin Oncol. 2013;31:57s.CrossRefGoogle Scholar
  30. 30.
    Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27:1160–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Lakhani AGR, Duan X, et al. Metabolic syndrome and recurrence within the 21-gene recurrence score assay risk categories in lymph node negative breast cancer. Cancer Res. 2012;72:144s.CrossRefGoogle Scholar
  32. 32.
    Pollan MPB, Martin M, et al. The effect of obesity on prognosis in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes. J Clin Oncol. 2013;31:56s.Google Scholar
  33. 33.
    Azambuja EDM-SW, Francis P, et al. 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. 2010;119:145–53.PubMedCrossRefGoogle Scholar
  34. 34.
    Dawood SLX, Litton JK. Impact of body mass index on survival outcome among women with early stage triple-negative breast cancer. Clinical Breast Cancer. 2012;12:364–72.PubMedCrossRefGoogle Scholar
  35. 35.
    Crozier JA, Moreno-Aspitia A, Ballman KV, et al. Effect of body mass index on tumor characteristics and disease-free survival in patients from the HER2-positive adjuvant trastuzumab trial N9831. Cancer. 2013;119:2447–54.PubMedCrossRefGoogle Scholar
  36. 36.
    Burstein HJ, Prestrud AA, Seidenfeld J, et al. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol Off J Am Soc Clini Oncol. 2010;28:3784–96.CrossRefGoogle Scholar
  37. 37.
    Sestak IDW, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: an exploratory analysis from the ATAC trail. J Clin Oncol. 2010;28:3411–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Ewertz MGK, Regan MM, et al. Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the Breast International Group 1-98 Trial. J Clin Oncol. 2012;30:3967–75.PubMedCrossRefGoogle Scholar
  39. 39.
    Pfeiler GKR, Fesl C, et al. 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. 2011;29:2653–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Geisler J, Haynes B, Anker G, et al. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol. 2002;20:751–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Jonat W, Mundhenke C. The FACE trial: letrozole or anastrozole as initial adjuvant therapy? Cancer Invest. 2007;25:14–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Yang Y, Yee D. Targeting insulin and insulin-like growth factor signaling in breast cancer. J Mammary Gland Biol Neoplasia. 2012;17:251–61.PubMedCrossRefGoogle Scholar
  43. 43.
    Col NFOL, Springmann V, et al. Metformin and breast cancer risk. Breast Cancer Res Treat. 2012;135:639–46.PubMedCrossRefGoogle Scholar
  44. 44.
    Goss PE, Ingle JN, Pritchard KI, et al. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27–a randomized controlled phase III trial. J Clin Oncol. 2013;31:1398–404.PubMedCrossRefGoogle Scholar
  45. 45.
    Goodwin PJSV. Obesity and insulin resistance in breast cancer - chemoprevention strategies with a focus on metformin. Breast. 2011;S3:S31–5.CrossRefGoogle Scholar
  46. 46.
    Goodwin PJ, Stambolic V, Lemieux J, et al. Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for clinical testing of anti-cancer agents. Breast Cancer Res Treat 126:215–20Google Scholar
  47. 47.
    Goodwin PJ PW, Gelmon KA, et al. Effect of metformin versus placebo on weight and metabolic factors in initial patients enrolled onto NCIC CTG MA.32, a multicenter adjuvant randomized controlled trial in early-stage breast cancer (BC). J Clin Oncol. 2013;31:57s.CrossRefGoogle Scholar
  48. 48.
    Bonanni B, Puntoni M, Cazzaniga M, et al. Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial. J Clin Oncol. 2012;30:2593–600.PubMedCrossRefGoogle Scholar
  49. 49.
    Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008;359:229–41.PubMedCrossRefGoogle Scholar
  50. 50.
    Ligibel JA, Strickler HD. Obesity and its impact on breast cancer. Am Soc Clin Oncol Educ Book. 2013;2013:52–9.CrossRefGoogle Scholar
  51. 51.
    Chlebowski RTBG, 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.PubMedCrossRefGoogle Scholar
  52. 52.
    Chlebowski R, Blackburn GL, Thomson C. Survival analyses from the Women’s Intervention Nutrition Study (WINS) evaluating dietary fat reduction and breast cancer outcome, American Society of Clinical Oncology. J Clin Oncol. 2008:Abst 522Google Scholar
  53. 53.
    Segal R, Pond G, Vallis M. Randomized trial of a lifestyle intervention for women with early-stage breast cancer (BC) receiving adjuvant hormone therapy: Initial results. J Clin Oncol. 2011;29:abstr 512.Google Scholar
  54. 54.
    Pierce JPNL, Caan BJ, et al. Influence of a diet very high in vegetables, fruit, fiber and low in fat on prognosis following treatment for breast cancer; the Women’s Healthy Eating and Living (WHEL) randomized trial. J Am Medical Assoc. 2007;298:289–98.CrossRefGoogle Scholar
  55. 55.
    Gannon MC, Nuttall FQ. Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes. Diabetes. 2004;53:2375–82.PubMedCrossRefGoogle Scholar
  56. 56.
    Hernandez TL, Sutherland JP, Wolfe P, et al. Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet. Am J Clin Nutr. 2010;91:578–85.PubMedCrossRefGoogle Scholar
  57. 57.
    Hwalla N, Shaker L, Torbay N, et al. Postprandial glycemic and insulinemic responses to high-carbohydrate vs high-protein meals in obese normoglycemic subjects with varied insulin sensitivity. Nutr Res. 2005;25:535–48.CrossRefGoogle Scholar
  58. 58.
    Nuttall FQ, Gannon MC, Saeed A, et al. The metabolic response of subjects with type 2 diabetes to a high-protein, weight-maintenance diet. J Clin Endocrinol Metab. 2003;88:3577–83.PubMedCrossRefGoogle Scholar
  59. 59.
    Meckling KA, O’Sullivan C, Saari D. Comparison of a low-fat diet to a low-carbohydrate diet on weight loss, body composition, and risk factors for diabetes and cardiovascular disease in free-living, overweight men and women. J Clin Endocrinol Metab. 2004;89:2717–23.PubMedCrossRefGoogle Scholar
  60. 60.
    Stern L, Iqbal N, Seshadri P, et al. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med. 2004;140:778–85.PubMedCrossRefGoogle Scholar
  61. 61.
    Fraser DA, Thoen J, Bondhus S, et al. Reduction in serum leptin and IGF-1 but preserved T-lymphocyte numbers and activation after a ketogenic diet in rheumatoid arthritis patients. Clin Exp Rheumatol. 2000;18:209–14.PubMedGoogle Scholar
  62. 62.
    Giovannucci E. Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J Clin Nutr. 2007;86:s836–42.PubMedGoogle Scholar
  63. 63.
    Stoll BA. Upper abdominal obesity, insulin resistance and breast cancer risk. Int J Obes Relat Metab Disord. 2002;26:747–53.PubMedCrossRefGoogle Scholar
  64. 64.
    Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–607.PubMedCrossRefGoogle Scholar
  65. 65.
    Foster GD, Wyatt HR, Hill JO, et al. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Ann Intern Med. 2010;153:147–57.PubMedCrossRefGoogle Scholar
  66. 66.
    Fine EJ, Segal-Isaacson CJ, Feinman RD, et al. Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. Nutrition. 2012;28:1028–35.PubMedCrossRefGoogle Scholar
  67. 67.
    Chlebowski R BG, Thomson C. Survival analyses from the Women’s Intervention Nutrition Study (WINS) evaluating dietary fat reduction and breast cancer outcome. J Clin Oncol. 2008:26.Google Scholar
  68. 68.
    Segal R PG, Vallis M. Randomized trial of a lifestyle intervention for women with early-stage breast cancer (BC) receiving adjuvant hormone therapy: Initial results. J Clin Oncol. 2011;29.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Rishi Jain
    • 1
  • Howard D. Strickler
    • 2
  • Eugene Fine
    • 3
  • Joseph A. Sparano
    • 4
    • 5
  1. 1.Department of MedicineMontefiore Medical Center, Albert Einstein College of MedicineBronxUSA
  2. 2.Department of Epidemiology and Population HealthMontefiore Medical Center, Albert Einstein College of MedicineBronxUSA
  3. 3.Department of Radiology, Division of Nuclear MedicineMontefiore Medical Center, Albert Einstein College of MedicineBronxUSA
  4. 4.Department of Medicine/OncologyMontefiore Medical Center, Albert Einstein College of MedicineBronxUSA
  5. 5.Weiler DivisionMontefiore Medical CenterBronxUSA

Personalised recommendations