title: Insulin use, hormone receptor status and hematopoietic cytokines׳ circulation in women with diabetes mellitus and breast cancer.
abstract: Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) are cytokines of particular interest in oncology from the perspective of neutropenia management (Mehta et al., 2015 [1]) and also as indirect activators of tumor-associated macrophages and modifiers of tumor microenvironment. Associated with poor breast cancer survival and unfavorable hormone receptor status (Wintrob et al., 2017 [2]), insulin may also influence hematopoiesis, thus interfering with colony stimulating factor production. Although G-CSF has been linked to exacerbating insulin resistance (Ordelheide et al., 2016 [3]), thus far no study linked insulin treatment and hematopoietic cytokines production. Additionally, IL-7 is the primary driver of T and B cell differentiation, maturation, and response (Corfe and Paige, 2012 [4]) and its elevated levels have been associated with poor prognosis in breast cancer. The data presented here is among the first to show a relationship between pre-existing use of injectable insulin in women diagnosed with breast cancer and type 2 diabetes mellitus, hematopoietic cytokine profiles at time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between G-CSF, GM-CSF, and IL-7 stratified by insulin use, controls, as well as by estrogen and progesterone receptor status is also provided.
authors.affiliation: State University of New York at Buffalo, Dept. of Pharmacy Practice, NYS Center of Excellence in Bioinformatics and Life Sciences, 701 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: Zachary A P
authors.initials: ZA
authors.lastname: Wintrob
authors.affiliation: Cleveland Clinic, Dept. of Biostatistics and Epidemiology, 9500 Euclid Ave., Cleveland, OH 44195, USA.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Hammel
authors.affiliation: State University of New York at Buffalo, Dept. of Pharmacy Practice, NYS Center of Excellence in Bioinformatics and Life Sciences, 701 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: George K
authors.initials: GK
authors.lastname: Nimako
authors.affiliation: State University of New York at Buffalo, Dept. of Biostatistics, 718 Kimball Tower, Buffalo, NY 14214, USA.
authors.forename: Dan P
authors.initials: DP
authors.lastname: Gaile
authors.affiliation: The UNC Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics, Campus Box 7569, Chapel Hill, NC 27599, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Forrest
authors.affiliation: State University of New York at Buffalo, Dept. of Pharmacy Practice, NYS Center of Excellence in Bioinformatics and Life Sciences, 701 Ellicott Street, Buffalo, NY 14203, USA; Roswell Park Cancer Institute, Dept. of Pharmacy Services, Elm & Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Alice C
authors.initials: AC
authors.lastname: Ceacareanu
keywords: Breast cancer; Cancer outcomes; Cancer prognosis; Diabetes; ER; Estrogen receptor; G-CSF; GM-CSF; Hematopoiesis; Hematopoietic cytokines; IL-7; Insulin; PR; Progesterone receptor