SpringerLink
Log in

Diabetes and prognosis in a breast cancer cohort

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Epidemiological studies indicated that type 2 diabetes mellitus may increase breast cancer risk and mortality. The aim of this retrospective cohort study was to examine the effect of diabetes on the clinical course and the prognosis of early stage breast cancer in relation to tumour and patient characteristics.

Methods

The cohort analyzed in this study consisted of 4,056 patients with invasive primary breast cancer. We compared overall survival, distant metastasis-free survival and local recurrence free survival between breast cancer patients with and without diabetes.

Results

In our cohort 276 breast cancer patients (6.8%) were affected by diabetes compared to 3,780 patients (93.2%) without diabetes. Women with diabetes were significantly older, had larger tumours, and a higher rate of lymph node involvement. After a follow-up period of 5 years, stratification for age and adjustment for other prognostic factors, overall mortality following breast cancer was significantly higher in diabetic breast cancer patients (hazard ratio, HR 1.92; 95% confidence interval, CI 1.49–2.48). We found no significant differences in distant metastasis-free survival and local recurrence free survival between the two groups, but we found a slightly significant higher rate of distant metastasis in the group of patients with diabetes and oestrogen receptor negative tumours (HR 2.28; CI 1.31–3.97).

Conclusion

In this study, patients with diabetes and oestrogen receptor negative breast cancer had a more than 2-fold higher risk for distant metastasis compared to patients without diabetes. Diabetes was also associated with an almost 2-fold increase in mortality within the 5 years follow-up period.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Barone BB, Yeh HC, Snyder CF, Peairs KS, Stein KB, Derr RL, Wolff AC, Brancati FL (2008) Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: A systematic review and meta-analysis. JAMA 300(23):2754–2764. doi:10.1001/jama.2008.824

    Article  PubMed  CAS  Google Scholar 

  • Blamey RW, Cataliotti L (2006) Eusoma accreditation of breast units. Eur J Cancer 42(10):1331–1337. doi:10.1016/j.ejca.2006.04.003

    Article  PubMed  CAS  Google Scholar 

  • Bray GA (1985) Obesity: definition, diagnosis and disadvantages. Med J Aust 142(7 Suppl):S2–S8

    PubMed  CAS  Google Scholar 

  • Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4(8):579–591. doi:10.1038/nrc1408

    Article  PubMed  CAS  Google Scholar 

  • Cardoso F, Castiglione M (2009) Locally recurrent or metastatic breast cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 20(Suppl 4):15–18. doi:10.1093/annonc/mdp115

    PubMed  Google Scholar 

  • Chlebowski RT, Blackburn GL, Buzzard IM, Rose DP, Martino S, Khandekar JD, York RM, Jeffery RW, Elashoff RM, Wynder EL (1993) Adherence to a dietary fat intake reduction program in postmenopausal women receiving therapy for early breast cancer. The women’s intervention nutrition study. J Clin Oncol 11(11):2072–2080

    PubMed  CAS  Google Scholar 

  • 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. doi:10.1093/jnci/djj494

    Article  PubMed  Google Scholar 

  • Chlebowski RT, Anderson G, Pettinger M, Lane D, Langer RD, Gilligan MA, Walsh BW, Chen C, McTiernan A (2008) Estrogen plus progestin and breast cancer detection by means of mammography and breast biopsy. Arch Intern Med 168(4):370–377. doi:10.1001/archinternmed.2007.123 (quiz 345)

    Article  PubMed  CAS  Google Scholar 

  • Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ (2004) Diabetes mellitus as a predictor of cancer mortality in a large cohort of us adults. Am J Epidemiol 159(12):1160–1167. doi:10.1093/aje/kwh161.159/12/1160

    Article  PubMed  Google Scholar 

  • 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. doi:10.1002/1097-0142(20010815)92:4<720::AID-CNCR1375>3.0.CO;2-T

    Article  PubMed  CAS  Google Scholar 

  • Del Giudice ME, Fantus IG, Ezzat S, McKeown-Eyssen G, Page D, Goodwin PJ (1998) Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat 47(2):111–120

    Article  PubMed  CAS  Google Scholar 

  • Eng-Wong J, Perkins SN, Bondy M, Li D, Eva Singletary S, Nunez N, Hursting S, Chang S (2009) Premenopausal breast cancer: estrogen receptor status and insulin-like growth factor-i (igf-i), insulin-like growth factor binding protein-3 (igfbp-3), and leptin. Breast J 15(4):426–428. doi:10.1111/j.1524-4741.2009.00753.x

    Article  PubMed  CAS  Google Scholar 

  • Feng YH, Velazquez-Torres G, Gully C, Chen J, Lee MH, Yeung SC (2010) The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth. J Cell Mol Med. doi:10.1111/j.1582-4934.2010.01083.x

  • Goodwin PJ, Boyd NF (1990) Body size and breast cancer prognosis: a critical review of the evidence. Breast Cancer Res Treat 16(3):205–214

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Grambsch PM, Therneau TM (1994) Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 81(3):515–526. doi:10.1093/biomet/81.3.515

    Article  Google Scholar 

  • Grote VA, Becker S, Kaaks R (2010) Diabetes mellitus type 2—an independent risk factor for cancer? Exp Clin Endocrinol Diabetes 118(1):4–8. doi:10.1055/s-0029-1243193

    Article  PubMed  CAS  Google Scholar 

  • Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE, Li J, Ho GY, Xue X, Anderson GL, Kaplan RC, Harris TG, Howard BV, Wylie-Rosett J, Burk RD, Strickler HD (2009) Insulin, insulin-like growth factor-i, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 101(1):48–60. doi:10.1093/jnci/djn415

    PubMed  CAS  Google Scholar 

  • Hjalgrim H, Frisch M, Ekbom A, Kyvik KO, Melbye M, Green A (1997) Cancer and diabetes—a follow-up study of two population-based cohorts of diabetic patients. J Intern Med 241(6):471–475

    Article  PubMed  CAS  Google Scholar 

  • Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN, Gonzalez-Angulo AM (2009) Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 27(20):3297–3302. doi:10.1200/JCO.2009.19.6410

    Article  PubMed  CAS  Google Scholar 

  • Kelsey JL, Berkowitz GS (1988) Breast cancer epidemiology. Cancer Res 48(20):5615–5623

    PubMed  CAS  Google Scholar 

  • Kleinberg DL, Wood TL, Furth PA, Lee AV (2009) Growth hormone and insulin-like growth factor-i in the transition from normal mammary development to preneoplastic mammary lesions. Endocr Rev 30(1):51–74. doi:10.1210/er.2008-0022

    Article  PubMed  CAS  Google Scholar 

  • Larsson SC, Mantzoros CS, Wolk A (2007) Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 121(4):856–862. doi:10.1002/ijc.22717

    Article  PubMed  CAS  Google Scholar 

  • LeRoith D, Novosyadlyy R, Gallagher EJ, Lann D, Vijayakumar A, Yakar S (2008) Obesity and type 2 diabetes are associated with an increased risk of develo** cancer and a worse prognosis; epidemiological and mechanistic evidence. Exp Clin Endocrinol Diabetes 116(Suppl 1):S4–S6. doi:10.1055/s-2008-1081488

    Article  PubMed  CAS  Google Scholar 

  • Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE (2008) The impact of diabetes on survival following breast cancer. Breast Cancer Res Treat 109(2):389–395. doi:10.1007/s10549-007-9654-0

    Article  PubMed  Google Scholar 

  • Michels KB, Solomon CG, Hu FB, Rosner BA, Hankinson SE, Colditz GA, Manson JE (2003) Type 2 diabetes and subsequent incidence of breast cancer in the nurses’ health study. Diabetes Care 26(6):1752–1758

    Article  PubMed  Google Scholar 

  • Patterson RE, Flatt SW, Saquib N, Rock CL, Caan BJ, Parker BA, Laughlin GA, Erickson K, Thomson CA, Bardwell WA, Hajek RA, Pierce JP (2010) Medical comorbidities predict mortality in women with a history of early stage breast cancer. Breast Cancer Res Treat. doi:10.1007/s10549-010-0732-3

  • Richardson LC, Pollack LA (2005) Therapy insight: Influence of type 2 diabetes on the development, treatment and outcomes of cancer. Nat Clin Pract Oncol 2(1):48–53. doi:10.1038/ncponc0062

    Article  PubMed  Google Scholar 

  • Rose DP, Vona-Davis L (2009) Influence of obesity on breast cancer receptor status and prognosis. Expert Rev Anticancer Ther 9(8):1091–1101. doi:10.1586/era.09.71

    Article  PubMed  CAS  Google Scholar 

  • Rose DP, Vona-Davis L (2010) Interaction between menopausal status and obesity in affecting breast cancer risk. Maturitas 66(1):33–38. doi:10.1016/j.maturitas.2010.01.019

    Article  PubMed  Google Scholar 

  • Singletary SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI, Borgen PI, Clark G, Edge SB, Hayes DF, Hughes LL, Hutter RV, Morrow M, Page DL, Recht A, Theriault RL, Thor A, Weaver DL, Wieand HS, Greene FL (2002) Revision of the American Joint Committee on Cancer Staging System for Breast Cancer. J Clin Oncol 20(17):3628–3636

    Article  PubMed  Google Scholar 

  • Stephenson GD, Rose DP (2003) Breast cancer and obesity: an update. Nutr Cancer 45(1):1–16

    Article  PubMed  CAS  Google Scholar 

  • Tsugane S, Inoue M (2010) Insulin resistance and cancer: epidemiological evidence. Cancer Sci. doi:10.1111/j.1349-7006.2010.01521.x

  • 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  PubMed  CAS  Google Scholar 

  • Verlato G, Zoppini G, Bonora E, Muggeo M (2003) Mortality from site-specific malignancies in type 2 diabetic patients from Verona. Diabetes Care 26(4):1047–1051

    Article  PubMed  Google Scholar 

  • Vona-Davis L, Howard-McNatt M, Rose DP (2007) Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer. Obes Rev 8(5):395–408. doi:10.1111/j.1467-789X.2007.00396.x

    Article  PubMed  CAS  Google Scholar 

  • Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000, projections for 2030. Diabetes Care 27(5):1047–1053

    Article  PubMed  Google Scholar 

  • Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B (2005) Diabetes mellitus and breast cancer. Lancet Oncol 6(2):103–111. doi:10.1016/S1470-2045(05)01736-5

    Article  PubMed  CAS  Google Scholar 

Download references

Competing interests

The authors declare no competing interests. The authors have full control of all primary data and allow the journal to review the data if requested.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University Hospital Erlangen, Erlangen, Germany

    Michael G. Schrauder, Lothar Häberle, Michael P. Lux, Claudia Rauh, Alexander Hein, Christian M. Bayer, Katharina Heusinger, Matthias W. Beckmann & Christian R. Loehberg

  2. Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Peter A. Fasching

  3. Institute of Pathology, University Hospital Erlangen, Erlangen, Germany

    Arndt Hartmann, Johanna D. Strehl & David L. Wachter

  4. Institute of Diagnostic Radiology, University Hospital Erlangen, Erlangen, Germany

    Rüdiger Schulz-Wendtland & Boris Adamietz

Authors
  1. Michael G. Schrauder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter A. Fasching
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lothar Häberle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael P. Lux
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Claudia Rauh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexander Hein
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christian M. Bayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Katharina Heusinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Arndt Hartmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Johanna D. Strehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. David L. Wachter
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Rüdiger Schulz-Wendtland
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Boris Adamietz
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Matthias W. Beckmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Christian R. Loehberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael G. Schrauder.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schrauder, M.G., Fasching, P.A., Häberle, L. et al. Diabetes and prognosis in a breast cancer cohort. J Cancer Res Clin Oncol 137, 975–983 (2011). https://doi.org/10.1007/s00432-010-0960-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-010-0960-2

Keywords

Search

Navigation