OPEN Research Support
head

Professor, Consultant
Henrik Ditzel
Department of Oncology, Odense University Hospital


Projekt styring
Projekt status    Sampling ongoing
 
Data indsamlingsdatoer
Start 01.02.2018  
Slut 31.10.2020  
 



Evaluation of biomarkers of sensitivity/resistance to endocrine therapy and CDK4/6 inhibitor in ER+ breast cancer

Short summary

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. 


Rationale

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.


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
  • Consultant Anne Marie Bak Jylling

Publications associated with the project

Protects Cells from Fulvestrant-Mediated Apoptosis and is a Predictor of Resistance to Fulvestrant in Estrogen Receptor-Positive Metastatic Breast Cancer. Alves CL, Elias D, Lyng M, Bak M, Kirkegaard T, Lykkesfeldt AE, et al. High CDK6 Clin Cancer Res 2016; 22: 5514-26