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Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis

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Abstract

Obesity is a risk factor for the development of new cases of breast cancer and also affects survival in women who have already been diagnosed with breast cancer. Early studies of obesity and breast cancer survival have been summarised in two meta-analyses, but the latest of these only included studies that recruited women diagnosed as recently as 1991. The primary aim of this study was to conduct a meta-analysis that included the more recent studies. A systematic search of MEDLINE, EMBASE and CINAHL was conducted to identify original data evaluating the effects of obesity on survival in newly diagnosed breast cancer patients. Adjusted hazard ratios (HR) from individual studies were pooled using a random effects model. A series of pre-specified sensitivity analyses were conducted on factors such as overall versus breast cancer survival and treatment versus observational cohort. The meta-analysis included 43 studies that enrolled women diagnosed with breast cancer between 1963 and 2005. Sample size ranged from 100 to 424168 (median 1192). The meta-analysis showed poorer survival among obese compared with non-obese women with breast cancer, which was similar for overall (HR = 1.33; 95% confidence interval (CI): 1.21, 1.47) and breast cancer specific survival (HR = 1.33; 95% CI: 1.19, 1.50). The survival differential varied only slightly, depending on whether body mass index (1.33; 1.21, 1.47) or waist–hip ratio (1.31; 1.08, 1.58) was used as the measure of obesity. There were larger differences by whether the woman was pre-menopausal (1.47) or post-menopausal (1.22); whether the cohort included women diagnosed before (1.31) or after 1995 (1.49); or whether the women were in a treatment (1.22) or observational cohort (1.36), but none of the differences were statistically significant. Women with breast cancer, who are obese, have poorer survival than women with breast cancer, who are not obese. However, no study has elucidated the causal mechanism and there is currently no evidence that weight loss after diagnosis improves survival. Consequently, there is currently no reason to place the additional burden of weight loss on women already burdened with a diagnosis of cancer. Further research should concentrate on assessing whether factors such as diabetes or type of chemotherapy modify the obesity effect and on understanding the causal mechanism, in particular the role of relative under-dosing.

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References

  1. 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):569–578

    Article  PubMed  Google Scholar 

  2. Vainio H, Kaaks R, Bianchini F (2002) Weight control and physical activity in cancer prevention, international evaluation of evidence: International Agency for Research on Cancer. Eur J Cancer Prev 11(Suppl 2):S94–S100

    PubMed  Google Scholar 

  3. van den Brandt P, Spiegleman D, Yaun S et al (2000) Pooled analysis of prospective cohort studies on height weight and breast cancer risk. Am J Epidemiol 152:514–527

    Article  PubMed  Google Scholar 

  4. Connolly BS, Barnett C, Vogt KN, Li T, Stone J, Boyd NF (2002) A meta-analysis of published literature on waist-to-hip ratio and risk of breast cancer. Nutr Cancer 44(2):127–138

    Article  PubMed  Google Scholar 

  5. Harvie M, Hooper L, Howell AH (2003) Central obesity and breast cancer risk: a systematic review. Obes Rev 4(3):157–173

    Article  CAS  PubMed  Google Scholar 

  6. Goodwin PJ, Esplen MJ, Winocur J, Butler K, Pritchard KI (1995) Development of a weight management program in women with newly diagnosed locoregional breast cancer. 11th international congress of psychosomatic obstetrics and gynaecology, Basel, Switzerland

  7. Ryu SY, Kim CB, Nam CM, Park JK, Kim KS, Park J et al (2001) Is body mass index the prognostic factor in breast cancer?: a meta-analysis. J Korean Med Sci 16(5):610–614

    CAS  PubMed  Google Scholar 

  8. Fleming TR, DeMets DL (1996) Surrogate end points in clinical trials: are we being misled? Ann Intern Med 125(7):605–613

    CAS  PubMed  Google Scholar 

  9. Pollock BH (2009) Cheaper, faster, better: chasing the elusive clinical trial end point. J Clin Oncol 27(17):2747–2748

    Article  PubMed  Google Scholar 

  10. Sridhara R, Johnson JR, Justice R, Keegan P, Chakravarty A, Pazdur R (2010) Review of oncology, hematology drug product approvals at the US Food, Drug Administration between July 2005, December 2007. J Natl Cancer Inst 102(4):230–243

    Article  PubMed  Google Scholar 

  11. 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):1467–1476

    CAS  PubMed  Google Scholar 

  12. Majed B, Moreau T, Asselain B (2009) Overweight, obesity and breast cancer prognosis: optimal body size indicator cut-points. Breast Cancer Res Treat 115(1):193–203

    Article  PubMed  Google Scholar 

  13. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  14. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 27(7414):557–560

    Article  Google Scholar 

  15. van Houwelingen HC, Arends LR, Stijnen T (2002) Advanced methods in meta-analysis: multivariate approach and meta-regression. Stat Med 21(4):589–624

    Article  PubMed  Google Scholar 

  16. Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56(2):455–463

    Article  CAS  PubMed  Google Scholar 

  17. StataCorp (2009) Stata/SE 10.1 for Windows. Stata Corporation, College Station, Texas, USA

  18. Reeves KW, Faulkner K, Modugno F, Hillier TA, Bauer DC, Ensrud KE et al (2007) Body mass index and mortality among older breast cancer survivors in the study of osteoporotic fractures. Cancer Epidemiol Biomarkers Prev 16(7):1468–1473

    Article  PubMed  Google Scholar 

  19. Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y et al (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20(1):42–51

    Article  CAS  PubMed  Google Scholar 

  20. 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):928–933

    CAS  PubMed  Google Scholar 

  21. Vitolins MZ, Kimmick GG, Douglas Case L (2008) BMI influences prognosis following surgery and adjuvant chemotherapy for lymph node positive breast cancer. Breast J 14(4):357–365

    Article  PubMed  Google Scholar 

  22. Ioannidis J, Lau J (2001) Evolution of treatment effects over time: empirical insight from recursive cumulative metaanalyses. Proc Natl Acad Sci USA 98(3):831–836

    Article  CAS  PubMed  Google Scholar 

  23. Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG et al (2006) Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet 368(9536):666–678

    Article  PubMed  Google Scholar 

  24. Borugian MJ, Sheps SB, Kim-Sing C, Olivotto IA, Van Patten C, Dunn BP et al (2003) Waist-to-hip ratio and breast cancer mortality. Am J Epidemiol 158(10):963–968

    Article  PubMed  Google Scholar 

  25. Abrahamson PE, Gammon MD, Lund MJ, Flagg EW, Porter PL, Stevens J et al (2006) General and abdominal obesity and survival among young women with breast cancer. Cancer Epidemiol Biomarkers Prev 15(10):1871–1877

    Article  PubMed  Google Scholar 

  26. Dal Maso L, Zucchetto A, Talamini R, Serraino D, Stocco CF, Vercelli M et al (2008) Effect of obesity and other lifestyle factors on mortality in women with breast cancer. Int J Cancer 123(9):2188–2194

    Article  CAS  PubMed  Google Scholar 

  27. Tao MH, Shu XO, Zhi XR, Gao YT, Zheng W (2006) Association of overweight with breast cancer survival. Am J Epidemiol 163(2):101–107

    Article  PubMed  Google Scholar 

  28. 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):123–133

    Article  CAS  PubMed  Google Scholar 

  29. Srokowski TP, Fang S, Hortobagyi GN, Giordano SH (2009) Impact of diabetes mellitus on complications and outcomes of adjuvant chemotherapy in older patients with breast cancer. J Clin Oncol 27(13):2170–2176

    Article  PubMed  Google Scholar 

  30. Egger M, Schneider M, Davey Smith G (1998) Spurious precision? Meta-analysis of observational studies. BMJ 316(7125):140–144

    CAS  PubMed  Google Scholar 

  31. Wee CC, McCarthy EP, Davis RB, Phillips RS (2004) Obesity and breast cancer screening. J Gen Intern Med 19(4):324–331

    Article  PubMed  Google Scholar 

  32. Dignam JJ, Mamounas EP (2004) Obesity and breast cancer prognosis: an expanding body of evidence. Ann Oncol 15(6):850–851

    Article  CAS  PubMed  Google Scholar 

  33. Li CI, Daling JR, Porter PL, Tang MT, Malone KE (2009) Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptor-positive invasive breast cancer. J Clin Oncol 27(32):5312–5318

    Article  PubMed  Google Scholar 

  34. de Azambuja E, McCaskill-Stevens W, Francis P, Quinaux E, Crown JP, Vicente M 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):145–153

    Article  PubMed  Google Scholar 

  35. Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4(8):579–591

    Article  CAS  PubMed  Google Scholar 

  36. Daling JR, Malone KE, Doody DR, Johnson LG, Gralow JR, Porter PL (2001) Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma. Cancer 92(4):720–729

    Article  CAS  PubMed  Google Scholar 

  37. Somasundar P, McFadden DW, Hileman SM, Vona-Davis L (2004) Leptin is a growth factor in cancer. J Surg Res 116(2):337–349

    Article  CAS  PubMed  Google Scholar 

  38. Hu X, Juneja SC, Maihle NJ, Cleary MP (2002) Leptin—a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst 94(22):1704–1711

    CAS  PubMed  Google Scholar 

  39. Tchernof A, Despres JP (2000) Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women. Horm Metab Res 2(11–12):526–536

    Article  Google Scholar 

  40. Lee CW, Norris B, Moravan V, Olivotto I (2003) Does body mass index influence the effectiveness of adjuvant tamoxifen in postmenopausal women with early stage breast cancer? Breast Cancer Res Treat 82(Suppl 1):(Abstr 309)

  41. Griggs JJ, Sorbero ME, Lyman GH (2005) Undertreatment of obese women receiving breast cancer chemotherapy. Arch Intern Med 165(11):1267–1273

    Article  PubMed  Google Scholar 

  42. Hunter RJ, Navo MA, Thaker PH, Bodurka DC, Wolf JK, Smith JA (2009) Dosing chemotherapy in obese patients: actual versus assigned body surface area (BSA). Cancer Treat Rev 35(1):69–78

    Article  CAS  PubMed  Google Scholar 

  43. Rosner GL, Hargis JB, Hollis DR, Budman DR, Weiss RB, Henderson IC et al (1996) 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 14(11):3000–3008

    CAS  PubMed  Google Scholar 

  44. Kotlyar M, Carson SW (1999) Effects of obesity on the cytochrome P450 enzyme system. Int J Clin Pharmacol Ther 37(1):8–19

    CAS  PubMed  Google Scholar 

  45. Barone BB, Yeh HC, Snyder CF, Peairs KS, Stein KB, Derr RL et al (2008) Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA 300(23):2754–2764

    Article  CAS  PubMed  Google Scholar 

  46. Chlebowski RT, Blackburn GL, Thomson CA, Nixon DW, Shapiro A, Hoy MK 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):1767–1776

    Article  PubMed  Google Scholar 

  47. Ballard-Barbash R, Hunsberger S, Alciati MH, Blair SN, Goodwin PJ, McTiernan A et al (2009) Physical activity, weight control, and breast cancer risk and survival: clinical trial rationale and design considerations. J Natl Cancer Inst 101(9):630–643

    Article  PubMed  Google Scholar 

  48. Barnett GC, Shah M, Redman K, Easton DF, Ponder BAJ, Pharoah PDP (2008) Risk factors for the incidence of breast cancer: do they affect survival from the disease? J Clin Oncol 26(20):3310–3316

    Article  PubMed  Google Scholar 

  49. 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):18–25

    CAS  PubMed  Google Scholar 

  50. Berclaz G, Li S, Price KN, Coates AS, Castiglione-Gertsch M, Rudenstam CM 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):875–884

    Article  CAS  PubMed  Google Scholar 

  51. Caan BJ, Kwan ML, Hartzell G, Castillo A, Slattery ML, Sternfeld B 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):1319–1328

    Article  PubMed  Google Scholar 

  52. Carmichael AR, Bendall S, Lockerbie L, Prescott RJ, Bates T (2004) Does obesity compromise survival in women with breast cancer? Breast 13(2):93–96

    Article  CAS  PubMed  Google Scholar 

  53. Chang S, Alderfer JR, Asmar L, Buzdar AU (2000) Inflammatory breast cancer survival: the role of obesity and menopausal status at diagnosis. Breast Cancer Res Treat 64(2):157–163

    Article  CAS  PubMed  Google Scholar 

  54. Cleveland RJ, Eng SM, Abrahamson PE, Britton JA, Teitelbaum SL, Neugut AI et al (2007) Weight gain prior to diagnosis and survival from breast cancer. Cancer Epidemiol Biomarkers Prev 16(9):1803–1811

    Article  PubMed  Google Scholar 

  55. Dawood S, Broglio K, Gonzalez-Angulo AM, Kau SW, Islam R, Hortobagyi GN et al (2008) Prognostic value of body mass index in locally advanced breast cancer. Clin Cancer Res 14(6):1718–1725

    Article  PubMed  Google Scholar 

  56. 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):129–137

    Article  Google Scholar 

  57. Dignam JJ, Wieand K, Johnson KA, Raich P, Anderson SJ, Somkin C 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):245–254

    Article  PubMed  Google Scholar 

  58. Eley JW, Hill HA, Chen VW, Austin DF, Wesley MN, Muss HB et al (1994) Racial differences in survival from breast cancer. Results of the National Cancer Institute Black/White Cancer Survival Study. JAMA 272(12):947–954

    Article  CAS  PubMed  Google Scholar 

  59. Enger SM, Bernstein L (2004) Exercise activity, body size and premenopausal breast cancer survival. Br J Cancer 90(11):2138–2141

    CAS  PubMed  Google Scholar 

  60. Ewertz M, Gillanders S, Meyer L, Zedeler K (1991) Survival of breast cancer patients in relation to factors which affect the risk of developing breast cancer. Int J Cancer 49(4):526–530

    Article  CAS  PubMed  Google Scholar 

  61. Greenberg ER, Vessey MP, McPherson K, Doll R, Yeates D (1985) Body size and survival in premenopausal breast cancer. Br J Cancer 51(5):691–697

    CAS  PubMed  Google Scholar 

  62. 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):17–28

    Article  CAS  PubMed  Google Scholar 

  63. Holmberg L, Lund E, Bergstrom R, Adami HO, Meirik O (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):351–354

    Article  CAS  PubMed  Google Scholar 

  64. Jain M, Miller AB (1994) Pre-morbid body size and the prognosis of women with breast cancer. Int J Cancer 59(3):363–368

    Article  CAS  PubMed  Google Scholar 

  65. Kroenke CH, Chen WY, Rosner B, Holmes MD (2005) Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol 23(7):1370–1378

    Article  PubMed  Google Scholar 

  66. Labidi SI, Mrad K, Mezlini A, Ouarda MA, Combes JD, Ben Abdallah M et al (2008) Inflammatory breast cancer in Tunisia in the era of multimodality therapy. Ann Oncol 19(3):473–480

    Article  CAS  PubMed  Google Scholar 

  67. Litton JK, Gonzalez-Angulo AM, Warneke CL, Buzdar AU, Kau SW, Bondy M et al (2008) Relationship between obesity and pathologic response to neoadjuvant chemotherapy among women with operable breast cancer. J Clin Oncol 26(25):4072–4077

    Article  PubMed  Google Scholar 

  68. Loi S, Milne RL, Friedlander ML, McCredie MRE, Giles GG, Hopper JL et al (2005) Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 14(7):1686–1691

    Article  PubMed  Google Scholar 

  69. Majed B, Moreau T, Senouci K, Salmon RJ, Fourquet A, Asselain B (2008) Is obesity an independent prognosis factor in woman breast cancer? Breast Cancer Res Treat 111(2):329–342

    Article  PubMed  Google Scholar 

  70. Mason BH, Holdaway IM, Stewart AW, Neave LM, Kay RG (1990) Season of tumour detection influences factors predicting survival of patients with breast cancer. Breast Cancer Res Treat 15(1):27–37

    Article  CAS  PubMed  Google Scholar 

  71. Mohle-Boetani JC, Grosser S, Whittemore AS, Malec M, Kampert JB, Paffenbarger RS Jr (1988) Body size, reproductive factors, and breast cancer survival. Prev Med 17(5):634–642

    Article  CAS  PubMed  Google Scholar 

  72. 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):5899–5905

    Article  PubMed  Google Scholar 

  73. 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):484–490

    Article  CAS  PubMed  Google Scholar 

  74. Nichols HB, Trentham-Dietz A, Egan KM, Titus-Ernstoff L, Holmes MD, Bersch AJ 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):1403–1409

    Article  PubMed  Google Scholar 

  75. Petrelli JM, Calle EE, Rodriguez C, Thun MJ (2002) Body mass index, height, and postmenopausal breast cancer mortality in a prospective cohort of US women. Cancer Causes Control 13(4):325–332

    Article  PubMed  Google Scholar 

  76. Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld B, Madlensky L 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):2345–2351

    Article  PubMed  Google Scholar 

  77. Reeves GK, Patterson J, Vessey MP, Yeates D, Jones L (2000) Hormonal and other factors in relation to survival among breast cancer patients. Int J Cancer 89(3):293–299

    Article  CAS  PubMed  Google Scholar 

  78. 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):1486–1491

    Article  CAS  PubMed  Google Scholar 

  79. Saxe GA, Rock CL, Wicha MS, Schottenfeld D (1999) Diet and risk for breast cancer recurrence and survival. Breast Cancer Res Treat 53(3):241–253

    Article  CAS  PubMed  Google Scholar 

  80. 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):641–646

    Article  CAS  PubMed  Google Scholar 

  81. Whiteman MK, Hillis SD, Curtis KM, McDonald JA, Wingo PA, Marchbanks PA (2005) Body mass and mortality after breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev 14(8):2009–2014

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. School of Population Health, The University of Queensland, Herston, QLD, 4006, Australia

    Melinda Protani

  2. Centre for HealthCare Improvement, Queensland Health, Brisbane, QLD, 4006, Australia

    Melinda Protani

  3. Cancer Council Victoria, Carlton, VIC, Australia, 3053

    Michael Coory

  4. Department of Medicine, Princess Alexandra Hospital, Woolloongabba, QLD, 4102, Australia

    Jennifer H. Martin

  5. Diamantina Institute and School of Medicine, The University of Queensland, Woolloongabba, QLD, 4102, Australia

    Jennifer H. Martin

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  1. Melinda Protani
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  2. Michael Coory
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Correspondence to Melinda Protani.

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All authors contributed to the design of the study and data extraction. MP performed the meta-analyses. All authors contributed to writing the paper.

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Protani, M., Coory, M. & Martin, J.H. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123, 627–635 (2010). https://doi.org/10.1007/s10549-010-0990-0

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