Professor, Consultant Henrik Ditzel Department of Oncology, Odense University Hospital
Projektet i tal
OPEN undersøgelse/kliniske data
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Evaluation of biomarkers of sensitivity/resistance to endocrine therapy and CDK4/6 inhibitor in ER+ breast cancer
We aim to investigate CDK6 and other proteins/genes as biomarkers for selection of patients who will benefit from the addition of CDK4/6 inhibitor to endocrine therapy. Furthermore, we aim to evaluate biomarkers predictive of resistance to CDK4/6 inhibitor, which will be identified and validated in preclinical models and in tumor samples from ER+ breast cancer patients treated with endocrine therapy and CDK4/6 inhibitor combination. \n
Breast tumors that express estrogen receptor (ER) represent the largest breast cancer subtype. Endocrine therapy has proven to be very effective in this subgroup of breast cancer, but a significant number of patients will eventually develop resistance to anti-hormonal agents. A wide range of pathways have been implicated in the mechanisms of resistance to endocrine therapy that have led to the development of several targeted inhibitors. CDK4/6 inhibitor and anti-hormonal combination therapy is already a new standard for the treatment of advanced ER+ breast cancer, and clinical trials evaluating the combination treatment in early stage breast cancer are ongoing. However, these inhibitors are costly, have toxic effects and some ER+ breast cancer patients derive strong clinical benefit from endocrine therapy alone. Therefore, clinicians need biomarkers that can identify patients that will fail anti-hormonal single therapy and, thus, may benefit from the addition of CDK4/6 inhibitor.
We have recently found that ER+ advanced breast cancer patients exhibiting high levels of CDK6 in their tumors respond poorly to the anti-estrogen fulvestrant and may benefit from the addition of CDK4/6 inhibitor to endocrine therapy. We aim to further investigate CDK6 as a biomarker for selection of patients who will benefit from the addition of CDK4/6 inhibitor to endocrine therapy. Furthermore, we aim to evaluate biomarkers predictive of resistance to CDK4/6 inhibitor, which will be identified and validated in preclinical models and in tumor samples from ER+ breast cancer patients treated with endocrine therapy and CDK4/6 inhibitor combination.
Description of the cohort
Approximately 200 women diagnosed with advanced ER+ breast cancer eligible for treatment with endocrine therapy and CDK4/6 inhibitor combination.\n
Data and biological material
We prospectively collect blood samples and FFPE/fresh frozen tumor biopsies before therapy and after disease progression.
We register clinical data regarding treatment regimens, response to treatment as well as data regarding immunohistochemic profile of both the primary tumor and the metastatic lesion.
Collaborating researchers and departments
Departments of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark
Postdoc Carla Alves, PhD
Postdoc Martina Tuttolomondo, PhD
Professor Henrik J. Ditzel
Department of Oncology, Odense University Hospital
Marianne Vogsen, MD
Jeanette D. Jensen, MD, PhD
Professor Marianne Ewertz
Professor Henrik J. Ditzel
Department of Clinical Pathology, Odense University Hospital