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Zhen Rong Siow,1–3 Richard H De Boer,2,3 Geoffrey J Lindeman,1–4 G Bruce Mann2–4 1ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, 2Department of Medical Oncology, Peter MacCallum Cancer Centre, 3Familial Cancer Centre, The Royal Melbourne Hospital, 4Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia Abstract: The Oncotype DX® assay was developed to address the need for optimizing the selection of adjuvant systemic therapy for patients with estrogen receptor (ER)-positive, lymph node-negative breast cancer. It has ushered in the era of genomic-based personalized cancer care for ER-positive primary breast cancer and is now widely utilized in various parts of the world. Together with several other genomic assays, Oncotype DX has been incorporated into clinical practice guidelines on biomarker use to guide treatment decisions. The Oncotype DX result is presented as the recurrence score which is a continuous score that predicts the risk of distant disease recurrence. The assay, which provides information on clinicopathological factors, has been validated for use in the prognostication and prediction of degree of adjuvant chemotherapy benefit in both lymph node-positive and lymph node-negative early breast cancers. Clinical studies have consistently shown that the Oncotype DX has a significant impact on decision making in adjuvant therapy recommendations and appears to be cost-effective in diverse health care settings. In this article, we provide an overview of the validation and clinical impact studies for the Oncotype DX assay. We also discuss its potential use in the neoadjuvant setting, as well as the more recent prospective validation trials, and the economic and utility implications of studies that use a lower cutoff score to define low-risk disease. Keywords: breast cancer, adjuvant, Oncotype DX®, recurrence score, utility

Christopher D Hart, Richard H De BoerDepartment of Oncology, Royal Melbourne Hospital, Victoria, AustraliaAbstract: Medullary thyroid cancer is an uncommon malignancy for which until recently little effective treatment existed. It is often characterized by mutation and overexpression of the receptor tyrosine kinases RET (rearranged during transfection), VEGFR2 (vascular endothelial growth factor receptor 2) and MET (mesenchymal-epithelial transition factor), which make attractive targets for drug development. Cabozantinib is an orally bioavailable tyrosine kinase inhibitor which blocks MET, VEGRF2 and RET, and has shown considerable activity in medullary thyroid cancer in a Phase III trial, including in heavily pretreated patients. Its novel combination of vascular endothelial growth factor and MET inhibition is believed to address the MET escape pathway, which is thought to be the cause of nonsustained tumor responses resulting from inhibition of vascular endothelial growth factor alone.Keywords: EXAM trial, VEGF escape pathways, MET, RET