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.
  
  
  RESULTS
  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.
authors.affiliation: Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands.|Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Heleen K
authors.initials: HK
authors.lastname: Bronsveld
authors.affiliation: Department of Pathology, Aarhus University Hospital THG, Aarhus, Denmark.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Jensen
authors.affiliation: Department of Pathology, Aarhus University Hospital THG, Aarhus, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Vahl
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, Utrecht, Netherlands.
authors.forename: Marie L
authors.initials: ML
authors.lastname: De Bruin
authors.affiliation: Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Sten
authors.initials: S
authors.lastname: Cornelissen
authors.affiliation: Division of Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Joyce
authors.initials: J
authors.lastname: Sanders
authors.affiliation: School of Public Health, University of Tampere, Tampere, Finland.
authors.forename: Anssi
authors.initials: A
authors.lastname: Auvinen
authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Haukka
authors.affiliation: Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Morten
authors.initials: M
authors.lastname: Andersen
authors.affiliation: Clinical Institute, Aalborg University, Aalborg, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Vestergaard
authors.affiliation: Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands.|Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Marjanka K
authors.initials: MK
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000145:classification* / Q000453:epidemiology* / Q000473:pathology; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause
chemical_list: D007328:Insulin