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Breast Cancer Research and Treatment

, Volume 151, Issue 3, pp 569–576 | Cite as

Obesity as an independent risk factor for decreased survival in node-positive high-risk breast cancer

  • Christoph ScholzEmail author
  • U. Andergassen
  • P. Hepp
  • C. Schindlbeck
  • Thomas W. P. Friedl
  • N. Harbeck
  • M. Kiechle
  • H. Sommer
  • H. Hauner
  • K. Friese
  • B. Rack
  • W. Janni
Clinical Trial

Abstract

Obese breast cancer patients have a higher risk of lymph node metastasis and a poorer prognosis compared to patients with normal weight. For obese women with node-positive breast cancer, an association between body weight and prognosis remains unclear. In this retrospective study, we analyzed patient data from the Phase-III ADEBAR trial, in which high-risk breast cancer patients (pT1–4, pN2–3, pM0) were randomized into a docetaxel-based versus epirubicin-based chemotherapy regimen. Patients were grouped according to their BMI value as underweight/normal weight (BMI < 25 kg/m2; n = 543), overweight (BMI 25–29.9 kg/m2; n = 482) or obese (BMI ≥ 30 kg/m2; n = 285). Overweight and obese patients were older, had larger tumors and were more likely to be postmenopausal at the time of diagnosis compared to underweight/normal-weight patients (all p < 0.001). Multivariate Cox regression analyses adjusting for age and histopathological tumor features showed that obese patients had a significantly shorter disease-free survival (DFS; HR 1.43; 95 % CI 1.11–1.86; p = 0.006) and overall survival (OS; HR 1.56; 95 % CI 1.14–2.14; p = 0.006) than non-obese patients. Subgroup analyses revealed that the differences in DFS and OS were significant for postmenopausal but not for premenopausal patients, and that the survival benefit of non-obese patients was more pronounced in women with hormone-receptor-positive disease. Obesity constitutes an independent, adverse prognostic factor in high-risk node-positive breast cancer patients, in particular for postmenopausal women and women with hormone-receptor-positive disease.

Keywords

Node-positive breast cancer Obesity Outcome 

Notes

Conflict of interest

All authors declare that there is no conflict of interest. W. Janni holds a consulting and advisory function at Sanofi-Aventis and Amgen.

Supplementary material

10549_2015_3422_MOESM1_ESM.pdf (78 kb)
Supplementary material 1 (PDF 78 kb)
10549_2015_3422_MOESM2_ESM.pdf (88 kb)
Supplementary material 2 (PDF 88 kb)
10549_2015_3422_MOESM3_ESM.pdf (88 kb)
Supplementary material 3 (PDF 87 kb)

References

  1. 1.
    Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH (2009) The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health 9:88CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Flegal KM, Graubard BI, Williamson DF, Gail MH (2007) Cause-specific excess deaths associated with underweight, overweight, and obesity. JAMA 298(17):2028–2037CrossRefPubMedGoogle Scholar
  3. 3.
    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
  4. 4.
    Cheraghi Z, Poorolajal J, Hashem T, Esmailnasab N, Doosti Irani A (2012) Effect of body mass index on breast cancer during premenopausal and postmenopausal periods: a meta-analysis. PLoS One 7(12):e51446CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Suzuki R, Orsini N, Saji S, Key TJ, Wolk A (2009) Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status—a meta-analysis. Int J Cancer 124(3):698–712CrossRefPubMedGoogle Scholar
  6. 6.
    Ursin G, Longnecker MP, Haile RW, Greenland S (1995) A meta-analysis of body mass index and risk of premenopausal breast cancer. Epidemiology 6(2):137–141CrossRefPubMedGoogle Scholar
  7. 7.
    Simpson ER, Brown KA (2013) Minireview: obesity and breast cancer: a tale of inflammation and dysregulated metabolism. Mol Endocrinol 27(5):715–725CrossRefPubMedGoogle Scholar
  8. 8.
    Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, Longcope C, Stanczyk FZ, Stephenson HE Jr, Falk RT, Miller R, Schatzkin A, Allen DS, Fentiman IS, Wang DY, Dowsett M, Thomas HV, Hankinson SE, Toniolo P, Akhmedkhanov A, Koenig K, Shore RE, Zeleniuch-Jacquotte A, Berrino F, Muti P, Micheli A, Krogh V, Sieri S, Pala V, Venturelli E, Secreto G, Barrett-Connor E, Laughlin GA, Kabuto M, Akiba S, Stevens RG, Neriishi K, Land CE, Cauley JA, Kuller LH, Cummings SR, Helzlsouer KJ, Alberg AJ, Bush TL, Comstock GW, Gordon GB, Miller SR (2003) Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95(16):1218–1226CrossRefPubMedGoogle Scholar
  9. 9.
    Maiti B, Kundranda MN, Spiro TP, Daw HA (2009) The association of metabolic syndrome with triple-negative breast cancer. Breast Cancer Res Treat 121(2):479–483CrossRefPubMedGoogle Scholar
  10. 10.
    Pierobon M, Frankenfeld CL (2012) Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat 137(1):307–314CrossRefPubMedGoogle Scholar
  11. 11.
    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
  12. 12.
    Ewertz M, Jensen MB, Gunnarsdottir KA, Hojris I, Jakobsen EH, Nielsen D, Stenbygaard LE, Tange UB, Cold S (2011) Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol 29(1):25–31CrossRefPubMedGoogle Scholar
  13. 13.
    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):627–635CrossRefPubMedGoogle Scholar
  14. 14.
    Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A, Navarro Rosenblatt D, Thune I, Vieira R, Norat T (2014) Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol 25(10):1901–1914CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Biglia N, Peano E, Sgandurra P, Moggio G, Pecchio S, Maggiorotto F, Sismondi P (2012) Body mass index (BMI) and breast cancer: impact on tumor histopathologic features, cancer subtypes and recurrence rate in pre and postmenopausal women. Gynecol Endocrinol 29(3):263–267CrossRefPubMedGoogle Scholar
  16. 16.
    Haakinson DJ, Leeds SG, Dueck AC, Gray RJ, Wasif N, Stucky CC, Northfelt DW, Apsey HA, Pockaj B (2012) The impact of obesity on breast cancer: a retrospective review. Ann Surg Oncol 19(9):3012–3018CrossRefPubMedGoogle Scholar
  17. 17.
    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):329–342CrossRefPubMedGoogle Scholar
  18. 18.
    Berclaz G, Li S, Price KN, Coates AS, Castiglione-Gertsch M, Rudenstam CM, Holmberg SB, Lindtner J, Erien D, Collins J, Snyder R, Thurlimann B, Fey MF, Mendiola C, Werner ID, Simoncini E, Crivellari D, Gelber RD, Goldhirsch A (2004) Body mass index as a prognostic feature in operable breast cancer: the International Breast Cancer Study Group experience. Ann Oncol 15(6):875–884CrossRefPubMedGoogle Scholar
  19. 19.
    de Azambuja E, McCaskill-Stevens W, Francis P, Quinaux E, Crown JP, Vicente M, Giuliani R, Nordenskjold B, Gutierez J, Andersson M, Vila MM, Jakesz R, Demol J, Dewar J, Santoro A, Lluch A, Olsen S, Gelber RD, Di Leo A, Piccart-Gebhart M (2009) 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):145–153CrossRefGoogle Scholar
  20. 20.
    Kamineni A, Anderson ML, White E, Taplin SH, Porter P, Ballard-Barbash R, Malone K, Buist DS (2012) Body mass index, tumor characteristics, and prognosis following diagnosis of early-stage breast cancer in a mammographically screened population. Cancer Causes Control 24(2):305–312CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Niraula S, Ocana A, Ennis M, Goodwin PJ (2012) Body size and breast cancer prognosis in relation to hormone receptor and menopausal status: a meta-analysis. Breast Cancer Res Treat 134(2):769–781CrossRefPubMedGoogle Scholar
  22. 22.
    Pajares B, Pollan M, Martin M, Mackey JR, Lluch A, Gavila J, Vogel C, Ruiz-Borrego M, Calvo L, Pienkowski T, Rodriguez-Lescure A, Segui MA, Tredan O, Anton A, Ramos M, Camara Mdel C, Rodriguez-Martin C, Carrasco E, Alba E (2013) Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis. Breast Cancer Res 15(6):R105CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Sparano JA, Wang M, Zhao F, Stearns V, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Fetting J, Davidson NE (2012) Obesity at diagnosis is associated with inferior outcomes in hormone receptor-positive operable breast cancer. Cancer 118(23):5937–5946CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Pan H, Gray R (2014) Effect of obesity in premenopausal ER+ early breast cancer: EBCTCG data on 80,000 patients in 70 trials. In: ASCO annual meeting abstract 503 present 31 May 2014Google Scholar
  25. 25.
    Chlebowski RT (2013) Nutrition and physical activity influence on breast cancer incidence and outcome. Breast 22(Suppl 2):S30–S37CrossRefPubMedGoogle Scholar
  26. 26.
    Goodwin PJ, Segal RJ, Vallis M, Ligibel JA, Pond GR, Robidoux A, Blackburn GL, Findlay B, Gralow JR, Mukherjee S, Levine M, Pritchard KI (2014) Randomized trial of a telephone-based weight loss intervention in postmenopausal women with breast cancer receiving letrozole: the LISA trial. J Clin Oncol 32(21):2231–2239CrossRefPubMedGoogle Scholar
  27. 27.
    Morey MC, Snyder DC, Sloane R, Cohen HJ, Peterson B, Hartman TJ, Miller P, Mitchell DC, Demark-Wahnefried W (2009) Effects of home-based diet and exercise on functional outcomes among older, overweight long-term cancer survivors: renew: a randomized controlled trial. JAMA 301(18):1883–1891CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    Reeves MM, Terranova CO, Eakin EG, Demark-Wahnefried W (2014) Weight loss intervention trials in women with breast cancer: a systematic review. Obes Rev 15(9):749–768CrossRefPubMedGoogle Scholar
  29. 29.
    Chlebowski RT, Blackburn GL, Thomson CA, Nixon DW, Shapiro A, Hoy MK, Goodman MT, Giuliano AE, Karanja N, McAndrew P, Hudis C, Butler J, Merkel D, Kristal A, Caan B, Michaelson R, Vinciguerra V, Del Prete S, Winkler M, Hall R, Simon M, Winters BL, Elashoff RM (2006) Dietary fat reduction and breast cancer outcome: interim efficacy results from the women’s intervention nutrition study. J Natl Cancer Inst 98(24):1767–1776CrossRefPubMedGoogle Scholar
  30. 30.
    Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, Rock CL, Kealey S, Al-Delaimy WK, Bardwell WA, Carlson RW, Emond JA, Faerber S, Gold EB, Hajek RA, Hollenbach K, Jones LA, Karanja N, Madlensky L, Marshall J, Newman VA, Ritenbaugh C, Thomson CA, Wasserman L, Stefanick ML (2007) Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the women’s healthy eating and living (WHEL) randomized trial. JAMA 298(3):289–298CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Rack B, Andergassen U, Neugebauer J, Salmen J, Hepp P, Sommer H, Lichtenegger W, Friese K, Beckmann MW, Hauner D, Hauner H, Janni W (2010) The German SUCCESS C study—the first european lifestyle study on breast cancer. Breast Care (Basel) 5(6):395–400CrossRefGoogle Scholar
  32. 32.
    Villarini A, Pasanisi P, Traina A, Mano MP, Bonanni B, Panico S, Scipioni C, Galasso R, Paduos A, Simeoni M, Bellotti E, Barbero M, Macellari G, Venturelli E, Raimondi M, Bruno E, Gargano G, Fornaciari G, Morelli D, Seregni E, Krogh V, Berrino F (2012) Lifestyle and breast cancer recurrences: the DIANA-5 trial. Tumori 98(1):1–18PubMedGoogle Scholar
  33. 33.
    Rock CL, Byers TE, Colditz GA, Demark-Wahnefried W, Ganz PA, Wolin KY, Elias A, Krontiras H, Liu J, Naughton M, Pakiz B, Parker BA, Sedjo RL, Wyatt H (2012) Reducing breast cancer recurrence with weight loss, a vanguard trial: the exercise and nutrition to enhance recovery and good health for you (ENERGY) trial. Contemp Clin Trials 34(2):282–295CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Christoph Scholz
    • 1
    Email author
  • U. Andergassen
    • 2
  • P. Hepp
    • 3
  • C. Schindlbeck
    • 4
  • Thomas W. P. Friedl
    • 1
  • N. Harbeck
    • 2
  • M. Kiechle
    • 5
  • H. Sommer
    • 2
  • H. Hauner
    • 6
  • K. Friese
    • 2
  • B. Rack
    • 2
  • W. Janni
    • 1
  1. 1.Frauenklinik der Universität UlmUlmGermany
  2. 2.Klinik und Poliklinik für Frauenheilkunde und GeburtshilfeLudwig-Maximilians-Universität München – Campus InnenstadtMunichGermany
  3. 3.FrauenklinikKlinikum der Heinrich-Heine-Universität DüsseldorfDüsseldorfGermany
  4. 4.Frauenklinik, Klinikum TraunsteinTraunsteinGermany
  5. 5.Frauenklinik, Klinikum rechts der Isar der Technischen Universitaet MuenchenMunichGermany
  6. 6.Else Kröner-Fresenius-Center for Nutritional MedicineTechnische Universität MünchenMunichGermany

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