Affiliations: Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Mexico | Becario de Posdoctorado en el Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública | Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico | Unidad de Investigación Biomédica en Cáncer, Subdirección de Investigación Básica, Instituto Nacional de Cancerología
Note: [] Correspondence to: Julieta Ivone Castro Romero, MD, PhD, Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad 655. Cuernavaca, Morelos, CP 62100, México. Tel.: +55 777 3293023; E-mail: [email protected]
Abstract: Obesity has reached epidemic proportions worldwide and is considered to be the fifth leading risk for death in the world, since it is associated with the development of a large number of chronic, non-communicable diseases, such as diabetes, cardiovascular disease, and a number of malignancies, including breast cancer. Thus, it is important to have knowledge of the changes in adipose tissue under conditions of obesity and to understand the mechanisms involved in the interactions between this tissue and the mammary gland which contribute to the development of breast cancer. The aim of this review was to present epidemiological and molecular evidence that supports some of the hypotheses related to the link between obesity, inflammation and breast cancer. Here we describe three main hypotheses: a) the interaction between obesity and breast cancer via androgen aromatization; 2) the increase of two mitogens such as insulin (hyperinsulinemia) and insulin-like growth factor (IGF) secondary to metabolic syndrome development by obesity and 3) the endocrine functions of adipocytes and their interactions with the immune system. In this review we analyze how some adipocytokines, such as leptin, adiponectin, and some cytokines such as tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6) and the plasminogen activator inhibitor 1 (PAI1) may function as risk factors for breast cancer development and show some evidence that explains the roll of inflammatory foci known “crown-like” structures (CLS) [constituted by dead adipocytes surrounded by macrophages M1 or M2] on breast cancer development, due to their ability to secrete and regulate different pro-inflammatory molecules (IL-1β, IL-6, TNFα) or anti-inflammatory protein (IL-10) involved in different cellular processes associated with carcinogenesis, such as proliferation, apoptosis, metastasis, invasion.
