Skip to main content

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

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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  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 9:88

    Article  PubMed Central  PubMed  Google Scholar 

  2. Flegal KM, Graubard BI, Williamson DF, Gail MH (2007) Cause-specific excess deaths associated with underweight, overweight, and obesity. JAMA 298(17):2028–2037

    Article  CAS  PubMed  Google Scholar 

  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):569–578

    Article  PubMed  Google Scholar 

  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):e51446

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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):698–712

    Article  CAS  PubMed  Google Scholar 

  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):137–141

    Article  CAS  PubMed  Google Scholar 

  7. Simpson ER, Brown KA (2013) Minireview: obesity and breast cancer: a tale of inflammation and dysregulated metabolism. Mol Endocrinol 27(5):715–725

    Article  CAS  PubMed  Google Scholar 

  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):1218–1226

    Article  CAS  PubMed  Google Scholar 

  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):479–483

    Article  PubMed  Google Scholar 

  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):307–314

    Article  PubMed  Google Scholar 

  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):1625–1638

    Article  PubMed  Google Scholar 

  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):25–31

    Article  PubMed  Google Scholar 

  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):627–635

    Article  PubMed  Google Scholar 

  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):1901–1914

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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):263–267

    Article  PubMed  Google Scholar 

  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):3012–3018

    Article  PubMed  Google Scholar 

  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):329–342

    Article  PubMed  Google Scholar 

  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):875–884

    Article  CAS  PubMed  Google Scholar 

  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):145–153

    Article  Google Scholar 

  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):305–312

    Article  PubMed Central  PubMed  Google Scholar 

  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):769–781

    Article  CAS  PubMed  Google Scholar 

  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):R105

    Article  PubMed Central  PubMed  Google Scholar 

  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):5937–5946

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 2014

  25. Chlebowski RT (2013) Nutrition and physical activity influence on breast cancer incidence and outcome. Breast 22(Suppl 2):S30–S37

    Article  PubMed  Google Scholar 

  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):2231–2239

    Article  PubMed  Google Scholar 

  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):1883–1891

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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):749–768

    Article  CAS  PubMed  Google Scholar 

  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):1767–1776

    Article  PubMed  Google Scholar 

  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):289–298

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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):395–400

    Article  Google Scholar 

  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):1–18

    CAS  PubMed  Google Scholar 

  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):282–295

    Article  PubMed Central  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christoph Scholz.

Additional information

Christoph Scholz and U. Andergassen have contributed equally.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Scholz, C., Andergassen, U., Hepp, P. et al. Obesity as an independent risk factor for decreased survival in node-positive high-risk breast cancer. Breast Cancer Res Treat 151, 569–576 (2015). https://doi.org/10.1007/s10549-015-3422-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-015-3422-3

Keywords

  • Node-positive breast cancer
  • Obesity
  • Outcome