title: Metabolic syndrome and pre-diabetes contribute to racial disparities in breast cancer outcomes: hypothesis and proposed pathways.
abstract: Women with obesity and type 2 diabetes (T2D) are at greater risk of dying from breast cancer than women without these conditions. Obesity and T2D are associated with insulin resistance and endogenous hyperinsulinemia and are more common in Black women. There is increasing disparity in breast cancer mortality between Black and White women in the USA. We hypothesize that insulin resistance and endogenous hyperinsulinemia in Black women with breast cancer contribute to their greater breast cancer mortality and are associated with increased insulin receptor signalling in tumours.
  
  
  
  We will recruit 350 Black women and 936 White women with newly diagnosed breast cancer. We will determine the presence or absence of the metabolic syndrome/pre-diabetes and insulin resistance by measuring body mass index, waist circumference, lipids, blood pressure, glucose, insulin-like growth factor binding protein 1 and insulin. Breast cancer prognosis will be determined by a Nottingham Prognostic Index (NPI), with poor prognosis being defined as NPI >4.4. Tumour insulin receptor signalling will be determined by immunohistochemistry. Insulin receptor subtype expression will be measured using Nanostring. Analysis of these factors will determine whether endogenous hyperinsulinemia is associated with a worse prognosis in Black women than White women and increased tumour insulin receptor signalling.
  
  
  
  The results of this study will determine if the metabolic syndrome and pre-diabetes contribute to racial disparities in breast cancer mortality. It may provide the basis for targeting systemic insulin resistance and/or tumour insulin receptor signalling to reduce racial disparities in breast cancer mortality. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Icahn School of Medicine at Mount Sinai, Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, New York, NY, USA. Emily.gallagher@mssm.edu.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Gallagher
authors.affiliation: Icahn School of Medicine at Mount Sinai, Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, New York, NY, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Population Health Science and Policy, Department of Medicine, New York, NY, USA.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Franco
authors.affiliation: Icahn School of Medicine at Mount Sinai, Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, New York, NY, USA.
authors.forename: Irini Markella
authors.initials: IM
authors.lastname: Antoniou
authors.affiliation: Icahn School of Medicine at Mount Sinai, Dubin Breast Cancer Center, Department of Pathology, New York, NY, USA.
authors.forename: Anupma
authors.initials: A
authors.lastname: Nayak
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Population Health Science and Policy, Department of Medicine, New York, NY, USA.|Center for Health Equity and Community Engaged Research, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Livaudais-Toman
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Population Health Science and Policy, Department of Medicine, New York, NY, USA.
authors.forename: Nina A
authors.initials: NA
authors.lastname: Bickell
mesh_terms: D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D054625:Healthcare Disparities; D006331:Heart Diseases / Q000209:etiology / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D011236:Prediabetic State / Q000150:complications*; D011379:Prognosis; D014481:United States / Q000453:epidemiology; D044465:White People / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: breast cancer; diabetes; insulin receptor; insulin resistance; metabolic syndrome; racial disparities