Rosette Lidereau, PhD

2009-2010 BCRF Project:
During the past two decades, the survival of breast cancer patients has greatly increased due to improvements in screening, early diagnosis and treatment selection. However, around 10% of patients with a diagnosis of early breast cancer will develop distant relapse, an event still deemed as a sign of incurable status despite a very heterogeneous course. Prognosis of this metastatic risk remains a critical issue in daily practice. Of the various prognostic markers available, none give an indication of the risk of metastasis to a specific organ. Such knowledge obtained at first diagnosis would help to plan care for patients, giving information to select new targets for emerging preventive treatments and contributing to avoid overtreatment in specific cases. The aims of this project are the identification and the molecular characterization of genes involved in breast cancer organ-specific metastasis. Such knowledge would help to plan care for patients, giving information to select new targets for emerging preventive treatments and contributing to avoid overtreatment in specific cases.

During the second period of the BCRF grant (February -May 2009), Dr. Lidereau analyzed at the RNA level a collection of up to 600 patients with breast tumors for molecular markers providing an assessment of patients at risk of developing metastases in the bone. In addition, her team evaluated their organ-specific metastasis signatures in the context of breast cancer subtypes. They have started the evaluation of selected "metastasis genes" at the protein level on a large scale basis by the RPPA (Reverse Phase Protein Arrays) technology. They further characterized the most relevant lung metastasis genes (FERMT1 and DSC2) at the functional level. Both genes increased the migratory and invasive properties when overexpressed in breast cancer cell lines. Moreover, FERMT1 was shown to play a key role in the epithelial-mesenchymal transition, a phenotype closely related to the invasive capacities of the cells. Finally, FERMT1 is currently being tested in different laboratory models.

The French researchers recently identified potential prognostic and diagnostic markers for organ-specific metastasis in human breast cancer, using oncogenomic techniques. Their new project aims to validate a small set of prognostic/diagnostic markers whose detection in the primary tumor or in sera, will provide an assessment of patients at risk of developing metastases in the bone, lung, liver and brain. Selected candidate genes will be screened in different cell-based assays (cell adhesion, invasion, migration and proliferation assays) to select those which will be the most potent at affect human breast cancer cell functions in vitro. These genes will next be tested in vivo using models of metastasis. Beside the enhancement of the understanding of the molecular mechanisms underlying the breast cancer metastasis development, this data might provide a potentially valuable tool to allow the clinicians to better define their breast cancer patients with higher risk to suffer from metastases. Finally, such knowledge might raise information to select new targets for emerging preventive treatments and contributing to avoid over-treatment in specific cases.

Bio:
Dr Rosette Lidereau received her PhD (1987) from Paris University, France. Since 1992 she is a Research Director of the INSERM (Institut National des Sciences et de la Recherche Médicale) and since 2000, she is in charge of the head of the INSERM Unit 735, located in the Centre René Huguenin (CRH), Saint-Cloud, France. CRH is a non-profit institution dedicated to cancer with a long medical and biological expertise in breast cancer.

She has developed her scientific career on biology of breast cancer within the CRH. Her former research interests are the evaluation of oncogenes implication in breast tumorigenesis and their impact in clinics as prognostic and predictive factors in breast cancer. Dr Rosette Lidereau is also the leader of the department of Oncogenetics in the CRH and contributes to the clinics with the diagnostic of cancer susceptibility genes mutations.

Since 2006, she is in charge of the constitution of the French database of BRCA mutations in collaboration of all French laboratories and the INCA (Institut National du Cancer). The INSERM Research U735 is devoted to Pharmacogenomics of Breast Cancer. Current research interests of the group are on the mechanisms of breast tumorigenesis, metastasis formation and the development of clinical application. It is a multidisciplinary group including scientists (molecular and cellular biology), clinicians and pathologists. The group has a long experience in the analysis of the molecular mechanisms leading to breast cancer progression mainly based on the study of several genes as molecular prognostic factors and predictive of therapy. In recent years, the group is leading an effort on mechanisms involved in site specific metastases in breast cancer. Dr Lidereau and her group has over 200 full-length publications in peer-reviewed journals.