Elsevier

The Lancet Oncology

Volume 6, Issue 2, February 2005, Pages 103-111
The Lancet Oncology

Review
Diabetes mellitus and breast cancer

https://doi.org/10.1016/S1470-2045(05)01736-5Get rights and content

Summary

Type 2 diabetes is a serious health problem that affects more than 7% of adults in developed countries. Up to 16% of patients with breast cancer have diabetes, and two major risk factors for type 2 diabetes—old age and obesity—are also associated with breast cancer. Three mechanisms have been postulated to associate diabetes with breast cancer: activation of the insulin pathway, activation of the insulin-like-growth-factor pathway, and regulation of endogenous sex hormones. Comparative cohort studies and case-control studies suggest that type 2 diabetes may be associated with 10–20% excess relative risk of breast cancer. Gestational diabetes mellitus, but not type 1 diabetes, might also be associated with excess risk of breast cancer. Moreover, diabetes and its complications can adversely affect cancer therapy and the use of screening, which will thus affect the outcome of patients with breast cancer.

Section snippets

Possible associations

Three mechanisms are thought to contribute to the association between type 2 diabetes and breast cancer: activation of the insulin pathway, activation of the insulin-like-growth-factor pathway, and impaired regulation of endogenous sex hormones.

Diabetes mellitus and risk of breast cancer

Different strategies have been used to define the possible association between diabetes mellitus and breast-cancer risk. We divided theses studies into three categories: cohort and case-control studies that type 2 diabetes; those that assessed blood concentrations of insulin-resistance markers (eg, glucose or insulin); and those that assessed other conditions, such as type 1 diabetes and gestational diabetes mellitus.

Insulin-resistance markers and breast cancer

Eight studies33, 39, 40, 41, 42, 43, 44, 45 have investigated the association between breast-cancer risk and fasting plasma concentrations of glucose, insulin, and C-peptide—all indirect markers of insulin resistance (table 1). Three studies were large cohort studies33, 40, 41 and five were case-control studies.39, 42, 43, 44, 45 Of the three studies33, 40, 42 that measured fasting glucose, only one case-control study42 reported an association between fasting glucose concentrations and

Risk in subgroups

Despite study of only small numbers of patients, a significant association between breast cancer in men and type 2 diabetes was reported in a cohort study30 and in a large case-control study (table 2).46 This association seems to be stronger compared with breast cancer in women and suggests a particular importance for the insulin pathway in the pathogenesis of breast cancer in men.

Gestational diabetes mellitus is the state of insulin resistance closely related to type 2 diabetes mellitus and

Effects of diabetes mellitus on outcome, diagnosis, and treatment

Diabetes can change the outcome of cancer either directly, through biological mechanisms, or indirectly, by affecting the use of screening and treatment allocation. Direct biological effects probably account for the inadequate outcome for patients with diabetes who have pancreatic cancer50 and hepatocellular carcinoma.51 Meyerhardt and co-workers52 analysed data from a large randomised controlled trial of adjuvant chemotherapy in colon cancer and showed that diabetes had direct adverse effects

Insulin treatment

Insulin treatment often results in very high plasma concentrations of insulin. However, despite the adverse effects in vitro and in vivo of insulin on breast cancer,11, 20 no association between insulin treatment and breast-cancer risk has been reported. In a study59 of 2720 patients with diabetes (most patients had type 2 diabetes) given insulin, no association between insulin treatment and cancer risk was found, irrespective of treatment duration or insulin dose. Furthermore, type 1 diabetes,

Screening of breast cancer in patients with diabetes

With current antidiabetic treatment, many patients with diabetes do not have additional comorbidity and thus may benefit from screening.65 However, a study66 in the USA reported that women with diabetes were significantly less likely to undergo screening mammography than were controls. The researchers suggested that both physicians and patients had a compromised attitude to preventive care in the setting of diabetes, and that the high costs of screening might also be a deterrent. Different

Breast-cancer treatment in patients with diabetes

Several well-known complications of diabetes, including nephropathy, neuropathy, heart disease, impaired wound healing, and susceptibility to infection, can adversely affect all forms of cancer therapy: surgical, radiation, chemotherapy, and hormonal therapy.

Conclusion

Data suggest that type 2 diabetes might be associated with up to 10–20% excess risk for breast cancer and that it could also have detrimental effects on the natural history, diagnosis, and treatment of breast cancer. However, because most epidemiological studies have not properly adjusted for several confounding factors, including obesity, other factors, not diabetes, might account for these observations. Diabetes mellitus might adversely affect decisions regarding breast-cancer screening and

Search strategy, selection criteria, and statistical analysis

Data for this review were identi.ed by searches of MEDLINE, PubMed, and references from relevant articles using the search terms “diabetes mellitus and breast cancer”, “diabetes mellitus and chemotherapy”, “diabetes mellitus and radiation therapy”, “diabetes mellitus and estrogen”, “breast cancer and insulin”, “breast cancer and IGF”, “breast cancer and obesity”, “breast cancer and comorbidity”, “MCF7 and insulin”, “breast cancer and PPARγ”, “breast cancer and biguanides”, and “breast

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