Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub‑phenotype ex vivo

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dc.article.end-page16en_ZA
dc.article.start-page1en_ZA
dc.citation.doi10.1038/s41598-020-75779-yen_ZA
dc.contributor.authorPather, Kyrtania
dc.contributor.authorAugustine, T. N.
dc.date.accessioned2021-07-27T09:06:57Z
dc.date.available2021-07-27T09:06:57Z
dc.date.issued2020-11-06
dc.descriptionSchool of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africaen_ZA
dc.description.abstractTamoxifen shows efficacy in reducing breast cancer-related mortality but clinically, is associated with increased risk for thromboembolic events. We aimed to determine whether breast tumour subphenotype could predict propensity for thrombosis. We present two ex vivo Models of Tamoxifentherapy, Model 1 in which treatment recapitulates accumulation within breast tissue, by treating MCF7 and T47D cells directly prior to exposure to blood constituents; and Model 2 in which we recreate circulating Tamoxifen by treating blood constituents prior to exposure to cancer cells. Blood constituents included whole blood, platelet-rich plasma and platelet-poor plasma. Hypercoagulation was assessed as a function of thrombin activity, expression of CD62P and CD63 activation markers defined as an index of platelet activation, and platelet morphology; while oestrogen receptor expression was assessed using immunocytochemistry with quantitative analysis. We determined, in concert with clinical studies and contrary to selected laboratory investigations, that Tamoxifen induces hypercoagulation, dependent on sub-phenotypes, with the T47D cell line capacity most enhanced. We determined a weak positive correlation between oestrogen receptor expression, and CD62P and CD63; indicating an association between tumour invasion profiles and hypercoagulation, however, other yet unknown factors may play a predictive role in defining hypercoagulation.en_ZA
dc.description.librarianLTM2021en_ZA
dc.facultyFaculty of Health Sciencesen_ZA
dc.funderWits Open Access Publishing Funden_ZA
dc.identifier.citationPather K, Augustine TN. Tamoxifen induces hypercoagulation and alterations in erα and erβ dependent on breast cancer sub-phenotype ex vivo. Scientific Reports. 2020;10(1):19256. DOI: 10.1038/s41598-020-75779-y.en_ZA
dc.identifier.issn2045-2322 (online)
dc.identifier.urihttps://hdl.handle.net/10539/31431
dc.journal.issue19256en_ZA
dc.journal.linkhttps://www.nature.com/srep/en_ZA
dc.journal.titleScientific Reportsen_ZA
dc.journal.volume10en_ZA
dc.language.isoenen_ZA
dc.publisherNatureen_ZA
dc.schoolSchool of Anatomical Sciencesen_ZA
dc.titleTamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub‑phenotype ex vivoen_ZA
dc.typeArticleen_ZA
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