Cancer and comorbidity: The role of leptin in breast cancer and associated pathologies

Abstract

Obesity is an important risk factor for postmenopausal breast cancer and also a poor prognostic factor among cancer patients. Moreover, obesity is associated with a number of health disorders such as insulin resistance/type-2 diabetes mellitus, hypertension, and other cardiovascular diseases. Frequently, these health disorders exhibit as components/complications of the metabolic syndrome. Nevertheless, obesity-related diseases may coexist with postmenopausal breast cancer; and these comorbid conditions could be substantial. Therefore, it may be assumed that different diseases including breast cancer could originate from a common pathological background in excessive adipose tissue. Adipocyte-released hormone-like cytokine (or adipokine) leptin behaves differently in a normal healthy state and obesity. A growing body of evidence suggests an important role of leptin in our major obesity-related health issues such as insulin resistance, hypertension, and neoplasia. In this context, this review describes the relationships of the abovementioned pathologies with leptin.

Impact of Adjuvant Treatment on Heparanase Concentration in Invasive, Unilateral Breast Cancer Patients: Results of a Prospective Single-Centre Cohort Study

“…Interestingly, overweight/obesity in postmenopausal women is associated with increased susceptibility to luminal breast cancers, but premenopausal overweight/obese women are more predisposed to developing triple-negative cancer. Thus, adiposity is linked to more aggressive breast cancer behaviours, including more advanced tumour stage and poor survival [ 23 , 24 ]. Hyperinsulinemia is a causal link between adiposity and breast cancer development.…”

Pre-Operative Combination of Normal BMI with Elevated YKL-40 and Leptin but Lower Adiponectin Level Is Linked to a Higher Risk of Breast Cancer Relapse: A Report of Four-Year Follow-Up Study

“…However, elevated leptin levels are associated with breast cancer aggressiveness and a bad prognosis. Leptin is believed to be involved in the growth and invasion of breast cancer cells by stimulating the conversion of aromatisable androgens (androstenedione and dehydroepiandrosterone) to oestradiol [ 4 , 11 ]. Therefore, the diminution of adiponectin (an anti-inflammatory adipokine) and exacerbation of leptin and YKL-40 (pro-inflammatory cytokines) in normal-weight breast cancer subjects may be associated with a more aggressive tumour phenotype.…”

“…Obesity leads to increased susceptibility for postmenopausal luminal breast cancers, but premenopausal obese women are more prone to developing a basal-like breast cancer (BLBC). Furthermore, adiposity is associated with a more aggressive breast cancer phenotype, including larger tumours, more often with nodal metastases and worse prognosis [ 3 , 4 , 5 , 6 ]. Thus, adiposity is linked with both cancer predisposition and cancer-dependent death [ 7 ].…”

Drosophila melanogaster: A Model Organism to Study Cancer

“…Obese people have often increased levels of circulating hormones like insulin that has been associated to higher levels of IGF-1 in colon, kidney, prostate and endometrial cancer (Roberts et al, 2010; Gallagher and LeRoith, 2015). Another hormone, leptin, a cytokine produced by the adipocytes to control satiety in a signaling circuit of the brain, has also been found up-regulated in tissues from obese people, particularly in women post-menopause, and increased levels of leptin have been associated with higher incidence of breast and other tumors (Ray, 2018). The adipose tissue produces pro-inflammatory cytokines including IL-6, IL-8, IFNγ, and TNF-α among others (Scheller et al, 2011; Arango Duque and Descoteaux, 2014), and their over-production in fats from obese, activates the infiltration of macrophages into the adipose tissue inducing a low level of chronic inflammation or adipocyte tissue macrophage infiltration called ATM (Lafontan, 2014; Kuroda and Sakaue, 2017).…”