Breast Cancer Research and Treatment

, Volume 150, Issue 3, pp 613–620 | Cite as

The association between diabetes and breast cancer stage at diagnosis: a population-based study

  • Lorraine L. LipscombeEmail author
  • Hadas D. Fischer
  • Peter C. Austin
  • Longdi Fu
  • R. Liisa Jaakkimainen
  • Ophira Ginsburg
  • Paula A. Rochon
  • Steven Narod
  • Lawrence Paszat


Women with diabetes have higher breast cancer incidence and mortality. The purpose of this study was to examine the impact of diabetes on stage at breast cancer diagnosis, as a possible reason for their higher mortality. Using population-based health databases from Ontario, Canada, this retrospective cohort study examined stage at diagnosis (II, III, or IV vs I) among women aged 20–105 years who were newly diagnosed with invasive breast cancer between 2007 and 2012. We compared those with diabetes to those without diabetes. Diabetes was defined based on medical records using a validated algorithm. Among 38,407 women with breast cancer, 6115 (15.9 %) women had diabetes. Breast cancer patients with diabetes were significantly more likely to present with advanced-stage breast cancer than those without diabetes. After adjustment for mammograms and other covariates, diabetes was associated with a significantly increased risk of Stage II [adjusted odds ratio (aOR) 1.14, 95 % confidence interval (CI) 1.07, 1.22], Stage III (aOR 1.21, 95 % CI 1.11, 1.33), and Stage IV (aOR 1.16, 95 % CI 1.01, 1.33) versus Stage I breast cancer. Women with diabetes had a higher risk of lymph node metastases (aOR 1.16, 95 % CI 1.06, 1.27) and tumors with size over 2 cm (aOR 1.16, 95 % CI 1.06, 1.28). Diabetes was associated with more advanced-stage breast cancer, even after accounting for differences in screening mammogram use and other factors. Our findings suggest that diabetes may predispose to more aggressive breast cancer, which may be a contributor to their higher cancer mortality.


Diabetes Breast cancer Stage at diagnosis Administrative databases 



Dr. Lipscombe is supported by a Canadian Institutes of Health Research (CIHR) New Investigator Award. Dr. Peter Austin is supported in part by a Career Investigator award from the Heart and Stroke Foundation. This study was conducted with the support from a CIHR operating Grant (MOP#123263), and from the Ontario Institute for Cancer Research and Cancer Care Ontario. This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual Grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript were the responsibilities of the authors. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material are based on data and information provided by Cancer Care Ontario. However, the analysis, conclusions, opinions and statements expressed herein are those of the authors and not necessarily those of Cancer Care Ontario. Dr. Lipscombe had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors would like to thank Lauren McNicol, MA, Women’s College Research Institute, for help with manuscript preparation.




  1. 1.
    Noto H et al (2011) Significantly increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Endocr. Pract. 17(4):616–628CrossRefPubMedGoogle Scholar
  2. 2.
    Barone BB et al (2008) Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA 300(23):2754–2764CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Peairs KS et al (2011) Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis. J. Clin. Oncol. 29(1):40–46CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Lipscombe LL et al (2008) The impact of diabetes on survival following breast cancer. Breast Cancer Res. Treat. 109(2):389–395CrossRefPubMedGoogle Scholar
  5. 5.
    Emerging Risk Factors C. et al, (2011) Diabetes mellitus, fasting glucose, and risk of cause-specific death. N. Engl. J. Med. 364(9):829–841CrossRefGoogle Scholar
  6. 6.
    van de Poll-Franse LV et al (2006) Increased health care utilisation among 10-year breast cancer survivors. Support Care Cancer 14(5):436–443CrossRefPubMedGoogle Scholar
  7. 7.
    Lee L et al (2011) Impact of comorbidity on chemotherapy use and outcomes in solid tumors: a systematic review. J. Clin. Oncol. 29(1):106–117CrossRefPubMedGoogle Scholar
  8. 8.
    Gross CP et al (2007) The impact of chronic illnesses on the use and effectiveness of adjuvant chemotherapy for colon cancer. Cancer 109(12):2410–2419CrossRefPubMedGoogle Scholar
  9. 9.
    Howlader N et al ((1975–2008)) SEER cancer statistics review. National Cancer Institute. Bethesda, MD. 2011 2011/08/20/.
  10. 10.
    Chan W et al (2014) Impact of socioeconomic status on breast cancer screening in women with diabetes: a population-based study. Diabet. Med. 31(7):806–812CrossRefPubMedGoogle Scholar
  11. 11.
    Lipscombe LL, Hux JE, Booth GL (2005) Reduced screening mammography among women with diabetes. Arch. Intern. Med. 165(18):2090–2095CrossRefPubMedGoogle Scholar
  12. 12.
    McBean AM, Yu X (2007) The underuse of screening services among elderly women with diabetes. Diabetes Care 30(6):1466–1472CrossRefPubMedGoogle Scholar
  13. 13.
    Beckman TJ et al (2001) Screening mammogram utilization in women with diabetes. Diabetes Care 24(12):2049–2053CrossRefPubMedGoogle Scholar
  14. 14.
    Jimenez-Garcia R et al (2009) Prevalence and predictors of breast and cervical cancer screening among Spanish women with diabetes. Diabetes Care 32(8):1470–1472CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Marshall JG et al (2010) Regional variations in cancer screening rates found in women with diabetes. Nurs. Res. 59(1):34–41CrossRefPubMedGoogle Scholar
  16. 16.
    Zhao G et al (2009) Prevalence and trends of receipt of cancer screenings among US women with diagnosed diabetes. J. Gen. Intern. Med. 24(2):270–275CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Hernandez AV et al (2014) Association between insulin resistance and breast carcinoma: a systematic review and meta-analysis. PLoS One 9(6):e99317CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Godsland IF (2010) Insulin resistance and hyperinsulinaemia in the development and progression of cancer. Clin. Sci. 118(5):315–332CrossRefGoogle Scholar
  19. 19.
    Lawlor DA, Smith GD, Ebrahim S (2004) Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women’s Heart and Health Study. Cancer Causes Control 15(3):267–275CrossRefPubMedGoogle Scholar
  20. 20.
    Belfiore A et al (2009) Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr. Rev. 30(6):586–623CrossRefPubMedGoogle Scholar
  21. 21.
    Milazzo G et al (1992) Insulin receptor expression and function in human breast cancer cell lines. Cancer Res. 52(14):3924–3930PubMedGoogle Scholar
  22. 22.
    De Meyts P et al (1995) Role of the time factor in signaling specificity: application to mitogenic and metabolic signaling by the insulin and insulin-like growth factor-I receptor tyrosine kinases. Metabolism 44(10 Suppl 4):2–11CrossRefPubMedGoogle Scholar
  23. 23.
    Fleming ST et al (2005) Comorbidity as a predictor of stage of illness for patients with breast cancer. Med. Care 43(2):132–140CrossRefPubMedGoogle Scholar
  24. 24.
    Srokowski TP et al (2009) Impact of diabetes mellitus on complications and outcomes of adjuvant chemotherapy in older patients with breast cancer. J. Clin. Oncol. 27(13):2170–2176CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    van de Poll-Franse LV et al (2007) Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis. Int. J. Cancer 120(9):1986–1992CrossRefPubMedGoogle Scholar
  26. 26.
    Hou G et al (2013) Clinical pathological characteristics and prognostic analysis of 1,013 breast cancer patients with diabetes. Breast Cancer Res. Treat. 137(3):807–816CrossRefPubMedGoogle Scholar
  27. 27.
    Yancik R et al (2001) Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA 285(7):885–892CrossRefPubMedGoogle Scholar
  28. 28.
    Taplin SH et al (2004) Reason for late-stage breast cancer: absence of screening or detection, or breakdown in follow-up? J. Natl. Cancer Inst. 96(20):1518–1527CrossRefPubMedGoogle Scholar
  29. 29.
    van Rossum LG et al (2009) Earlier stages of colorectal cancer detected with immunochemical faecal occult blood tests. Neth. J. Med. 67(5):182–186PubMedGoogle Scholar
  30. 30.
    Robles SC et al (1988) An application of capture-recapture methods to the estimation of completeness of cancer registration. J. Clin. Epidemiol. 41(5):495–501CrossRefPubMedGoogle Scholar
  31. 31.
    Cancer Care Ontario (2009) Appendix C2 - Stage: Frequently Asked Questions. Accessed 9 Dec 2013
  32. 32.
    Hux JE et al (2002) Diabetes in Ontario: determination of prevalence and incidence using a validated administrative data algorithm. Diabetes Care 25(3):512–516CrossRefPubMedGoogle Scholar
  33. 33.
    Canadian Task Force on Preventive Health Care: Screening for breast cancer: recommendations for clinicians and policy-makers. Health, Canada (2011)Google Scholar
  34. 34.
    Austin PD, Henderson SE (2011) Biopsychosocial assessment criteria for functional chronic visceral pain: a pilot review of concept and practice. Pain Med. 12(4):552–564CrossRefPubMedGoogle Scholar
  35. 35.
    Lipscombe LL, Hux JE (2007) Trends in diabetes prevalence, incidence, and mortality in Ontario, Canada 1995–2005: a population-based study. Lancet 369(9563):750–756CrossRefPubMedGoogle Scholar
  36. 36.
    S.I. Inc., (2011) Base SAS® 9.3 Procedures Guide. SAS Institute Inc.: CaryGoogle Scholar
  37. 37.
    Smith U, Gale EA (2010) Cancer and diabetes: are we ready for prime time? Diabetologia 53(8):1541–1544CrossRefPubMedGoogle Scholar
  38. 38.
    Stein KB et al (2010) Colorectal cancer outcomes, recurrence, and complications in persons with and without diabetes mellitus: a systematic review and meta-analysis. Dig. Dis. Sci. 55(7):1839–1851CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Renehan AG et al (2012) Diabetes and cancer (2): evaluating the impact of diabetes on mortality in patients with cancer. Diabetologia 55(6):1619–1632CrossRefPubMedGoogle Scholar
  40. 40.
    Kerlikowske K et al (2008) Obesity, mammography use and accuracy, and advanced breast cancer risk. J. Natl. Cancer Inst. 100(23):1724–1733CrossRefPubMedCentralPubMedGoogle Scholar
  41. 41.
    Geiss LS et al (2014) Prevalence and incidence trends for diagnosed diabetes among adults aged 20 to 79 years, United States, 1980–2012. JAMA 312(12):1218–1226CrossRefPubMedGoogle Scholar
  42. 42.
    Iqbal J et al (2015) Differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity in the United States. JAMA 313(2):165–173CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Lorraine L. Lipscombe
    • 1
    • 2
    • 3
    • 4
    Email author
  • Hadas D. Fischer
    • 3
  • Peter C. Austin
    • 3
    • 4
  • Longdi Fu
    • 3
  • R. Liisa Jaakkimainen
    • 3
    • 5
    • 6
  • Ophira Ginsburg
    • 1
    • 2
    • 4
  • Paula A. Rochon
    • 1
    • 2
    • 3
    • 4
  • Steven Narod
    • 1
    • 2
  • Lawrence Paszat
    • 3
    • 4
    • 6
  1. 1.Women’s College Research InstituteWomen’s College HospitalTorontoCanada
  2. 2.Department of MedicineUniversity of TorontoTorontoCanada
  3. 3.Institute for Clinical Evaluative SciencesTorontoCanada
  4. 4.Institute of Health Policy, Management and EvaluationUniversity of TorontoTorontoCanada
  5. 5.Department of Family and Community MedicineUniversity of TorontoTorontoCanada
  6. 6.Sunnybrook Health Sciences CentreTorontoCanada

Personalised recommendations