Insulin use, hormone receptor status and hematopoietic cytokines׳ circulation in women with diabetes mellitus and breast cancer

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.