TY - JOUR

T1 - Diabetes and breast cancer subtypes

AU - Bronsveld, Heleen K

AU - Jensen, Vibeke

AU - Vahl, Pernille

AU - De Bruin, Marie L.

AU - Cornelissen, Sten

AU - Sanders, Joyce

AU - Auvinen, Anssi

AU - Haukka, Jari

AU - Andersen, Morten

AU - Vestergaard, Peter

AU - Schmidt, Marjanka K

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background Women 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 Findings This 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. Conclusions We 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.

AB - Background Women 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 Findings This 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. Conclusions We 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.

UR - http://www.scopus.com/inward/record.url?scp=85009174948&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0170084

DO - 10.1371/journal.pone.0170084

M3 - Journal article

C2 - 28076434

AN - SCOPUS:85009174948

VL - 12

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 1

M1 - e0170084

ER -