Emily J Gallagher1, Derek LeRoith2, Rebeca Franco3, Irini Markella Antoniou2, Anupma Nayak4, Jennifer Livaudais-Toman3,5, Nina A Bickell3. 1. 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. 2. Icahn School of Medicine at Mount Sinai, Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, New York, NY, USA. 3. Icahn School of Medicine at Mount Sinai, Department of Population Health Science and Policy, Department of Medicine, New York, NY, USA. 4. Icahn School of Medicine at Mount Sinai, Dubin Breast Cancer Center, Department of Pathology, New York, NY, USA. 5. Center for Health Equity and Community Engaged Research, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
BACKGROUND: 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. METHODS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. CONCLUSIONS: 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.
Authors: Katrine L Henriksen; Birgitte B Rasmussen; Anne E Lykkesfeldt; Susann Møller; Bent Ejlertsen; Henning T Mouridsen Journal: J Clin Pathol Date: 2006-06-14 Impact factor: 3.411
Authors: Kimberly S Peairs; Bethany B Barone; Claire F Snyder; Hsin-Chieh Yeh; Kelly B Stein; Rachel L Derr; Frederick L Brancati; Antonio C Wolff Journal: J Clin Oncol Date: 2010-11-29 Impact factor: 44.544
Authors: Bette J Caan; Marilyn L Kwan; Georgina Hartzell; Adrienne Castillo; Martha L Slattery; Barbara Sternfeld; Erin Weltzien Journal: Cancer Causes Control Date: 2008-08-28 Impact factor: 2.506
Authors: I Balslev; C K Axelsson; K Zedeler; B B Rasmussen; B Carstensen; H T Mouridsen Journal: Breast Cancer Res Treat Date: 1994 Impact factor: 4.872
Authors: Rosalyn D Ferguson; Ruslan Novosyadlyy; Yvonne Fierz; Nyosha Alikhani; Hui Sun; Shoshana Yakar; Derek Leroith Journal: Breast Cancer Res Date: 2012-01-07 Impact factor: 6.466
Authors: Temidayo Fadelu; Ruth Damuse; Joarly Lormil; Elizabeth Pecan; Lauren Greenberg; Cyrille Dubuisson; Viergela Pierre; Scott A Triedman; Lawrence N Shulman; Timothy R Rebbeck Journal: JCO Glob Oncol Date: 2020-10