Diabetes and breast cancer subtypes

Heleen K Bronsveld; Vibeke Jensen; Pernille Vahl; Marie L. De Bruin; Sten Cornelissen; Joyce Sanders; Anssi Auvinen; Jari Haukka; Morten Andersen; Peter Vestergaard; Marjanka K Schmidt

doi:10.1371/journal.pone.0170084

Diabetes and breast cancer subtypes

Heleen K Bronsveld, Vibeke Jensen, Pernille Vahl, Marie L. De Bruin, Sten Cornelissen, Joyce Sanders, Anssi Auvinen, Jari Haukka, Morten Andersen, Peter Vestergaard, Marjanka K Schmidt

20 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e0170084
Journal	PLOS ONE
Volume	12
Issue number	1
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0170084
Publication status	Published - 1 Jan 2017
Externally published	Yes

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title = "Diabetes and breast cancer subtypes",

abstract = "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.",

author = "Bronsveld, {Heleen K} and Vibeke Jensen and Pernille Vahl and {De Bruin}, {Marie L.} and Sten Cornelissen and Joyce Sanders and Anssi Auvinen and Jari Haukka and Morten Andersen and Peter Vestergaard and Schmidt, {Marjanka K}",

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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

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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.

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Diabetes and breast cancer subtypes

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