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
ReviewDiabetes mellitus and 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
References (75)
New perspectives into the molecular pathogenesis and treatment of type 2 diabetes.
Cell
(2001)- et al.
Epidemiology of breast cancer.
Lancet Oncol
(2001) - et al.
Diabetes mellitus and cancer
Eur J Intern Med
(2000) - et al.
Insulin/insulin-like growth factor-I and estrogen cooperate to stimulate cyclin E-Cdk2 activation and cell cycle progression in MCF-7 breast cancer cells through differential regulation of cyclin E and p21(WAF1/Cip1)
J Biol Chem
(2001) - et al.
Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis
Lancet
(2004) - et al.
Preoperative core needle biopsy as an independent risk factor for wound infection after breast surgery
Obstet Gynecol
(2003) - et al.
The impact of diabetes mellitus on the toxicity of therapy for advanced ovarian cancer
Gynecol Oncol
(1996) - et al.
Epidemiology of endometrial cancer
Best Pract Res Clin Obstet Gynaecol
(2001) Diagnosis and classification of diabetes mellitus
Diabetes Care
(2004)Age- and sex-specific prevalences of diabetes and impaired glucose regulation in 13 European cohorts
Diabetes Care
(2003)