(P03-010-24) Effects of Biophysical Properties of Extracellular Vesicles and Tumor Subtype on Bone Integrity Loss in Breast Cancer Survivors

Objectives: To assess the biophysical properties of extracellular vesicles as possible mediators of bone integrity loss in breast cancer survivors according to the immunohistochemical subtype of their tumors.

Methods: A secondary analysis of the data produced during a study with a quasi-experimental design where breast cancer survivors were recruited at diagnosis and received a nutritional intervention along with the first six months of antineoplastic treatment was performed. Among the data used from the original study were body composition measurements including bone densitometry by dual-energy X-ray absorptiometry and stored plasma samples that were used to isolate EV by using ExoQuick®. The EV were characterized by light scattering techniques, electron microscopy, and ExoCheck®. Mixed-effects linear regression models were used to evaluate the associations between variables, adjusting for confounders and testing the Kenny and Baron conditions for mediation variables. Sobel Test was used to assess the significance of the mediation effect.

Results: 16 BCS fulfilled the selection criteria to be enrolled in the secondary analysis. Two populations of EV with different sizes were found. BCS who were premenopausal at the beginning of the study had a 3.1% loss in their lumbar spine bone mineral density (BMD), while in those who were postmenopausal had a loss of 4.8% at femoral neck’s BMD. The direct effect of tumor subtypes on lumbar spine BMD (βc=-0.139; p< 0.01) and bone mineral content of femoral neck (βc=0.693; p=0.05) were higher after adjusting for the average hydrodynamic diameter (AD_h) of the large EV population) (respectively: βc’= 0.144; p< 0.01; βc’=1.011, p< 0.01). Despite all these effects were significant, the indirect effects were not (respectively: βaβb=-0.029, p=0.12; y βaβb=0.304, p=0.26).

Conclusions: These findings suggest that the size of a larger EV could have a suppression effect over a mediator of bone integrity loss in breast cancer survivors according to the immunohistochemical subtype of their tumors. However, studies with larger samples are needed to prove this.

Funding Sources: Consejo Nacional de Humanidades, Ciencias y Tecnología (CONAHCYT