Endocrine Abstracts

Introduction: Obesity and insulin resistance have been identified as risk factors for breast cancer and are associated with late-stage diagnosis and poor prognosis. Ghrelin is a unique gut-derived peptide that has major impact in energy homeostasis and weight regulation, with new emerging implications in tumorigenesis process, especially in hormone-dependent cancers.

Aim: To evaluate the relationship between ghrelin, clinico-biological parameters of obesity and gonadotropic axis in breast cancer patients.

Patients and Methods: We assessed the relationship between fasting ghrelin and anthropometric measures, insulin-resistance, lipid and glucose metabolism parameters, hypothalamic-pituitary-gonadal axis (HPG): FSH, testosterone/estradiol-ratio, SHBG, and body composition (evaluated by dual-energy X-ray absorptiometry) in 64 breast cancer patients. Both acyl-ghrelin (AG) and des-acyl-ghrelin (DAG) were evaluated through ELISA; total ghrelin (TG) was calculated as the sum of the two.

Results: DAG, but not AG, negatively correlates with BMI (r=−0.280, P=0.013), waist circumference (r=−0.335, P=0.006) and waist/hip ratio (r=−0.302, P=0.015). Concerning body fat distribution, DAG negatively correlates with sub-total (r=−0.326, P=0.005) and truncal fat mass (r=−0.273, P=0.02). Even stronger association of these parameters was observed with TG. Also, DAG negatively correlates with insulin l (r=−0.354, P=0.003) and HOMA-IR (r=−0.343, P=0.004). Concerning HPG, AG, but especially AG/TG-ratio were positively correlated with FSH (r=0.354, P=0.004) and SHBG (r=0.272, P=0.03). Even though no direct correlations were found between ghrelin and HPG, we observed that insulin positively correlates with testosterone/estradiol-ratio (r=0.247, P=0.039), as with SHBG (P=0.341, P=0.004), and that the hip circumference was positively correlated with free-testosterone levels (r=0.251, P=0.044).

Conclusions: Ghrelin has definitely indirect effects in breast cancer through its roles in obesity and insulin-resistance. We described different connections between ghrelin-obesity-gonadotropic axis in these patients, underlying discreet metabolic and hormonal modifications. However, ghrelin may also play a direct role in breast cancer pathogenesis due to its recently discovered anti-aromatase effect in adipocytes.