Modelling the procoagulatory effect of Anastrozole relative to ER alpha and ER beta expression in breast cancer cells

摘要

Background Anastrozole is commonly used for the treatment of oestrogen receptor (ER)-positive breast cancer but can increase thromboembolic risk. It is unclear if ER presentation is associated with platelet-mediated hypercoagulation. We investigated the relationship between hypercoagulation and ER alpha and ER beta expression in breast cancer cell lines under Anastrozole treatment. Methods In Model 1, MCF-7 or T47D cancer cells were treated with Anastrozole, then exposed to whole blood and platelet-rich plasma, modelling platelet engagement in the tumour bed. In Model 2, blood components were treated with Anastrozole, then exposed to cancer cells, modelling circulatory effects in the vasculature. Hypercoagulation was assessed as a combined function of thrombin activity, platelet CD62P and CD63 expression, and corresponding platelet ultrastructure. Tumour ER alpha and ER beta were immunolocalised and following quantification assessed for correlation with hypercoagulatory parameters. Results Anastrozole enhanced hypercoagulation in both Models and cell lines. T47D cells induced more distinct features of hypercoagulation and responded by heightening ER beta expression and sustaining expression of ER alpha, indicative of a more aggressive phenotype. Post-exposure to cell lines, CD62P and CD63 expression correlated, but this was not maintained following Anastrozole treatment. Substantive correlations could not be found explaining the changes in ER expression and hypercoagulatory parameters, indicating unknown causative factors. Conclusion These results provide basic science evidence showing that the hypercoagulatory effects induced by Anastrozole treatment may be related to the tumour subphenotype. Clinical studies are required to determine whether tracking of hypercoagulatory parameters may hold value in describing subphenotypic alterations or metastatic potential during tumour progression.