Abstract
BackgroundWomen with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes.Methods and FindingsThis cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000–2010. Stratified by age at breast cancer diagnosis (≤50 and >50 years), women with diabetes were 2:1 frequency-matched on year of birth and age at breast cancer diagnosis (both in 10-year categories) to women without diabetes, to select ~300 patients with tumor tissue available. Tumor MicroArrays were stained by immunohistochemistry for estrogen and progesterone receptor (ER, PR), HER2, Ki67, CK5/6, CK14, and p63. A pathologist scored all stains and revised morphology and grade. Associations between diabetes/insulin treatment and clinicopathological subtypes were analyzed using multivariable logistic regression. Morphology and grade were not significantly different between women with diabetes (n = 211) and women without diabetes (n = 101), irrespective of menopausal status. Premenopausal women with diabetes tended to have more often PR-negative (OR = 2.44(95%CI:1.07–5.55)), HER2-negative (OR = 2.84(95%CI:1.11–7.22)), and basal-like (OR = 3.14(95%CI:1.03–9.60) tumors than the women without diabetes, with non-significantly increased frequencies of ER-negative (OR = 2.48(95%CI:0.95–6.45)) and triple negative (OR = 2.60(95%CI:0.88–7.67) tumors. After adjustment for age and BMI, the associations remained similar in size but less significant. We observed no evidence for associations of clinicopathological subtypes with diabetes in postmenopausal women, or with insulin treatment in general.ConclusionsWe found no compelling evidence that women with diabetes, treated with or without insulin, develop different breast cancer subtypes than women without diabetes. However, premenopausal women with diabetes tended to develop breast tumors that do not express hormonal receptors, which are typically associated with poor prognosis.
Highlights
Diabetes mellitus and breast cancer are chronic diseases with increasing incidence in many countries [1,2]
We found no compelling evidence that women with diabetes, treated with or without insulin, develop different breast cancer subtypes than women without diabetes
Premenopausal women with diabetes tended to develop breast tumors that do not express hormonal receptors, which are typically associated with poor prognosis
Summary
Diabetes mellitus and breast cancer are chronic diseases with increasing incidence in many countries [1,2]. Women with diabetes have a 15–20% increased risk of breast cancer compared to women without diabetes [6,7,8,9], but no impact of insulin analogue treatment has been shown [5]. Overall mortality after breast cancer diagnosis has been shown to be 30–60% higher in women with diabetes compared to women without diabetes [11,12,13,14,15,16], even after adjustment for tumor stage [13,14,16]. Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes
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