Adipokines in Plasma and Breast Tissues: Associations with Breast Cancer Risk Factors

Abstract

Background Blood adipokines are associated with breast cancer risk; however, blood–breast adipokine correlations and factors that explain variation in adipokines are unknown. Methods Plasma (n = 155) and breast (n = 85) leptin and adiponectin were assessed by immunoassays in women with no history of cancer. Multivariable-adjusted regression models were used to determine breast adipokine associations. Results Through body mass index (BMI)-adjusted analyses, we initially observed positive plasma–breast correlations for leptin (r = 0.41, P = 0.0002) and adiponectin (r = 0.23, P = 0.05). The positive plasma–breast correlation for leptin was strongest among normal weight women (r = 0.62), whereas the correlation for adiponectin was strongest among obese women (r = 0.31). In multivariable models, adjusting for BMI, demographic, reproductive, and lifestyle factors, plasma leptin was not associated with breast leptin, and only the highest quartile of plasma adiponectin was associated with tissue levels. Of the risk factors investigated, those that contributed most to the variation in breast tissue adipokines were BMI and race for leptin, oral contraceptive use and smoking status for adiponectin. Conclusions Although we report positive plasma–breast adipokine correlations overall, plasma adipokine concentrations may not be good surrogates for breast concentrations among all women. Predictors of breast adipokines vary, depending on subject characteristics, possibly explaining inconsistent epidemiologic results and they implicate differing pathways toward carcinogenesis. Impact A clearer understanding of the relationships between plasma adipokines and their levels within the target organ is necessary to better understand the impact of these hormones on breast cancer risk. Future studies are needed to identify additional factors associated with breast adipokines in target tissues.

A Case-Controlled Study of the Oncologic Safety of Fat Grafting

“…Concern was raised that placement of these physiochemical factors at the site of a previous tumour microenvironment, may fuel the 'tumour-stromal interaction' through autocrine, paracrine and exocrine/endocrine that can result in tumour recurrence 14,[56][57][58][59][60][61][64][65][66] and metastasis 58,67,68 Local and systemic recurrence of breast cancer is observed at similar rates in our case controlled series, and may occur irrespective of the fat grafting intervention. Local recurrence and metastasis may be a manifestation of residual cancer stem cell activation and dissemination for reasons largely unknown, although the underlying molecular microenvironment may play a role 56,60,73 .…”

“…Adipocytes and ASCs release cytokines ('adipokines') to communicate with resident tissue for stimulating angiogenesis, reducing apoptosis, and modulating the immune response during tissue repair 57,58,60,61 . The initial apprehension regarding FG and cancer resurgence came from obesity studies observing altered adipokine signaling in resident adipocytes that could facilitate cancer initiation and progression 62,62 .…”

“…The initial apprehension regarding FG and cancer resurgence came from obesity studies observing altered adipokine signaling in resident adipocytes that could facilitate cancer initiation and progression 62,62 . These 'adipokines' have been extensively studied, and include; leptin, adiponectin, resistin, metalloproteinase 11, hepatocyte growth factor (HGF), adipocytederived collagen VI, Interleukins, TGR-a, TGF-b, and VEGF 57,58,[60][61][62][63][64] .…”

“…Local recurrence and metastasis may be a manifestation of residual cancer stem cell activation and dissemination for reasons largely unknown, although the underlying molecular microenvironment may play a role 56,60,73 . Long term dormancy of cancer cells is a known phenomenon, but it is particularly evident in breast cancer patients in whom, even after 8 years of disease-free survival, a significant rate of late recurrence has been observed 74,75 .…”

Serum Adiponectin but not Leptin at Diagnosis as a Predictor of Breast Cancer Survival

“…A casecontrol study nested within the Multiethnic cohort (MEC) found an increased risk of postmenopausal breast cancer among women with the highest prediagnostic levels of leptin among normal weight women (Ollberding et al, 2013). A recent study examining the relationship of leptin in the circulation and in the breast tissue of healthy women (Llanos et al, 2012), reported correlation for leptin r=0.62(p=0.009) for normal women, r=0.36 (p=0.08) for overweight women, and r=0.03 (p=0.86) for obese women. In an analysis conducted in the Northern Sweden Health and Disease Cohort (Cust et al, 2009), the association between prediagnostic leptin and the risk of breast cancer differed by the stage at diagnosis with an inverse association reported for early stage and a suggestive positive association reported late stage disease when examined among pre-and postmenopausal combined.…”