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Advanced Stages of Breast Cancer and Type 2 Diabetes

Mar 5, 2019
 
Editor: Joy Pape, MSN, FNP-C, CDE, WOCN, CFCN, FAADE

Author: Dahlia Elimairi, Pharm D Student, UC Denver Skaggs School of Pharmacy

Women with type 2 diabetes are at increased risk of developing breast cancer.

A new nested case-control study in a retrospective breast cancer cohort was performed that suggests that women with type 2 diabetes are at increased risk to be diagnosed with a more aggressive type of breast cancer than women without diabetes.

It is still unclear what the association between diabetes and breast cancer are and whether improvements in diabetes care can reduce the increased mortality in patients with breast cancer. Several mechanisms have been suggested for the increased risk of breast cancer in women with type 2 diabetes, such as obesity, the specific metabolic derangements of diabetes itself, including hyperglycemia, hyperinsulinemia, and insulin resistance, and the use of insulin and specifically insulin analogs. Patients with breast cancer and diabetes tend to present at later stages.

This study was published January 29, 2019 in Diabetes Care and investigated whether women with type 2 diabetes developed a more advanced stage of breast cancer and whether treatment with insulin analogs is associated with specific breast cancer characteristics. Women with breast cancer diagnosed in 2002-2014 were selected from the linked Netherlands Cancer Registry-PHARMO Database Network. Women with breast cancer and with type 2 diabetes were matched and compared with women with breast cancer and without diabetes. Also, women with type 2 diabetes using insulin analogs were compared with women with type 2 diabetes not using insulin analogs and where unmatched. Multivariable ordinal logistic regression was used to investigate the association between type 2 diabetes/insulin and breast cancer characteristics.

The study concluded that type 2 diabetes was associated with more advanced stages of breast cancer. Women with type 2 diabetes were at increased risk of being diagnosed with a larger tumor, a more advanced lymph node status, a more advanced tumor stage and a higher grade, but at decreased risk of being diagnosed with a progesterone receptor negative tumor than women without diabetes. Among women with type 2 diabetes, no differences in any pathologic breast cancer characteristic were found between the insulin analog users and the noninsulin analog users.

Few studies have investigated whether the use of insulin analogs was associated with breast cancer. From these studies H.K. Bronsveld, et al and L. Mu, et al had the same findings as this new study where there was no association between insulin use and breast cancer. One study by H. Goldvaser et al found insulin usage was associated with a higher rate of angiolymphatic invasion, although this was based on nine insulin users only, thus data regarding this matter is conflicting and sparse and therefore there is no reason to restrain the use of insulin in women with type 2 diabetes due to the risk of breast cancer.

Another retrospective cohort study examined the effect of diabetes on the clinical course and the prognosis of early stage breast cancer in relation to tumor and patient characteristics. The study compared overall survival, distant metastasis-free survival, and local recurrence-free survival between breast cancer patients with and without diabetes. The study found that patients with diabetes and estrogen 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-year follow-up period.

Evidence regarding the association between breast cancer and diabetes is scarce, but the majority is consistent with the findings of this new study.

Practice Pearls:

  • The majority of evidence available suggests increased risk of more aggressive breast cancer in patients with type 2 diabetes compared to patients with no diabetes.
  • Further research is needed to strengthen these results and to investigate if improvements in diabetes care can reduce risk of breast cancer in patients with type 2 diabetes.
  • Based on the current evidence, there is no reason to restrain the use of insulin analog among women with type 2 diabetes with regard to its effects on breast cancer subtype and expected subsequent prognosis.

References:

Overbeek JA, van Herk-Sukel MPP, Vissers PAJ, van der Heijden AAWA, Bronsveld  HK, Herings RMC, Schmidt MK, Nijpels G. Type 2 Diabetes, but Not Insulin (Analog) Treatment, Is Associated With More Advanced Stages of Breast Cancer: A National Linkage of Cancer and Pharmacy Registries. Diabetes Care. 2019 Jan 24.

Bronsveld HK, Jensen V, Vahl P, et al. Diabetes and breast cancer subtypes. PLoS One 2017;12: e0170084.

Mu L, Zhu N, Zhang J, Xing F, Li D, Wang X. Type 2 diabetes, insulin treatment and prognosis of breast cancer. Diabetes Metab Res Rev 2017; 33:e2823.

Goldvaser H, Rizel S, Hendler D, et al. The association between treatment for metabolic disorders and breast cancer characteristics. Int J Endocrinol 2016;2016:4658469.

Schrauder MG, Fasching PA, Häberle L, Lux MP, Rauh C, Hein A, Bayer CM,

Heusinger K, Hartmann A, Strehl JD, Wachter DL, Schulz-Wendtland R, Adamietz B, Beckmann MW, Loehberg CR. Diabetes and prognosis in a breast cancer cohort. J Cancer Res Clin Oncol. 2011 Jun;137(6):975-83.

Dahlia Elimairi, Pharm D Student, UC Denver Skaggs School of Pharmacy