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Protein biomarker for the prediction of response to endocrine treatment in breast cancer patients

Final Report Summary - ENDOPREDICT (Protein biomarker for the prediction of response to endocrine treatment in breast cancer patients)

Classical pathologic parameters have been used to inform adjuvant clinical treatment choices for early breast cancer patients. There remains a significant number of patients however, who despite a reportedly favourable prognostic profile, experience metastatic disease. Elucidation of the mechanisms of tumour adaptability and the identification of predictive markers of early recurrence is the basis of personalized medicine.
Work from our group has established the developmental protein HOXC11 as a powerful predictor of resistance to endocrine treatment in breast cancer patients. The aim of this project was to establish a joint industry-academia partnership to produce a commercially viable and clinically validated predictive assay/kit which is based on the use of HOXC11 as a predictive biomarker of poor response to endocrine treatment in breast cancer patients. We have developed an automated monclonal HOXC11 immunohistochemistry assay to industry standards and migrated to a high through-put system ready for use in pathology departments. Analytical validation of the assay at two independent sites has been completed. The resultant assay has an accuracy of 95.4%, sensitivity of 96.6%, specificity of 96.4% and reproducibility of 91.3%.
In order to clinically validate the monclonal HOXC11 immunohistochemistry assay we have completed a retrospective clinical trial. We have used a training set of 560 breast cancer patients to set a clinically relevant cut off for the assay which enabled the prediction of response to endocrine treatment with disease free survival periods as read-out. Using a validation cohort of patients (n=300 patients), the clinical utility of the HOXC11 assay was confirmed.
For clinical validation of the HOXC11 monoclonal antibody assay patients were recruited onto the ICORG, ‘Breast Cancer Proteomics and Molecular Heterogeneity’, ICORG 07-09 which was initiated in January 2008 and amended in February 2013 (NCT01840293)S33. To date >1,500 patients have been recruited to this trial, >800 were recruited over the lifetime of the IAPP (February 2013-January 2017). HOXC11 status was assessed in these trial patients using the analytically validated HOXC11 assay. A second clinical validation study consisting of a 2,000 breast cancer patient cohort from Nottingham, UK has now been completed.
A commercialization plan was developed by Almac Diagnostics along with the Technical Transfer Office at RCSI to bring the clinical HOXC11 monoclonal antibody assay to market. A Technology Summary detailing the analytical and clinical characteristics and outlining the features and benefits of the technology was prepared. International pharma and biomarker companies were contacted with regard to licencing opportunities for this technology. Preparation of publication of this work is now underway to promote licencing opportunities.
Further details are available on the website contact person Leonie Young.