Martine J. Piccart-Gebhart, MD, PhD

2012-2013 BCRF Project:
(made possible by generous support from EMD Millipore)

The Breast International Group (BIG) launched a comprehensive program to integrate clinical trial data as well as to provide access to multi-scale information from breast cancer trials conducted throughout Europe and by other BIG member groups around the world. There are two main needs in the current climate of multi-national clinical trials: first, to facilitate research using data from multiple completed clinical trials; and secondly, to bring an efficient molecular screening service from a few key European laboratories to multiple hospitals.

To fully utilize the volume of data derived from clinical trials, researchers need to be able to retrieve temporal (e.g. before and after therapy) and multi-level (e.g. from microarray data, clinical data to MRI/PET) data from specific population groups (e.g. pre- or postmenopausal women) with specific characteristics (e.g. that have received specific therapy regime). These trials serve as tremendous resources, as researchers will then be able to extract from the data predictive biomarkers or develop models and answer such research questions as "Can these models or biomarkers help predict the specific therapy outcome for a patient in order to avoid unnecessary/costly treatment?"

In addition, as genomic technology advances and scientists are able to identify important molecular aberrations relevant for novel drugs, the need to implement a "molecular screening service" for clinical trials increases. BCRF support has been used to set up the pilot INTEGRATE Molecular Screening Study, which provides such needed screening services. In 2012-2013, BIG will expand the INTEGRATE Molecular Screening Pilot Study to include metastatic patients. Adding this component will bring with it a set of different challenges from those encountered in the (neo)-adjuvant setting. It is clear that relapsing tumors can acquire new molecular mutations from the original breast cancer, and treatment decisions can vary depending on which result is taken.

Acquisition of such biopsies from metastatic sites requires more intensive multidisciplinary planning and baseline and post-treatment evaluation requires the availability of paired radiological images. The INTEGRATE pilot study will be expanded to accommodate the complex interactions between multidisciplinary teams, allow paired analyses to compare mutational differences within any individual patient; and the information technology platform will be adapted to handle raw radiological images.

Mid-year Progress: The Molecular Screening PILOT Study has shifted its focus to the setting of metastatic breast cancer with an aim to accrue 30 patients with advanced disease. There is emerging evidence demonstrating molecular heterogeneity existing between primary and metastatic tumors, although the clinical significance of this is not well defined. It is plausible that one of the keys to improving the outcomes of patients with metastatic disease could be in selecting treatment against mutational targets identified through screening of actual metastases, rather than the primary tumors. This Molecular Screening PILOT Study therefore has been modified to mandate the collection of metastatic biopsies in order to perform the molecular tests. The IT infrastructure to support this study has been completed, the laboratories are ready to receive samples and the clinical centers are currently undergoing protocol activation. Results of this study will be available within six months.

Bio:
Dr. Piccart is Professor of Oncology at the Université Libre de Bruxelles (ULB) and Director of Medicine at the Jules Bordet Institute, in Brussels, Belgium. Earning her medical degrees at the ULB and oncology qualifications in New York and London, she is also member of the Belgian Royal Academy of Medicine. With a primary interest in breast cancer and drug development, Dr. Piccart is a leader in international research collaboration, and is the principal or co-principal investigator of many clinical trials, including HERA, MINDACT, and ALTTO. She is co-founder and chair of the Breast International Group (BIG), uniting 50 academic research groups from around the world and running over 30 trials under its umbrella. BIG's research programs include NeoBIG, an innovative biomarker and drug development program focused on neo-adjuvant trials. It also included the European Commission-supported TRANSBIG consortium of 29 institutions in 11 countries (running with the European Organization for Research and Treatment of Cancer's MINDACT trial), which ended in February 2011. Dr. Piccart is active in numerous professional organizations, currently serving as president-elect of European Society of Medical Oncology. She is immediate past-president of the EORTC and served on the American Society of Clinical Oncology Board. (Co) author of more than 300 publications in peer-reviewed journals, she has received numerous prestigious awards for her research contributions, including most recently in 2009, BCRF's Jill Rose Award and the William L. McGuire Award at the San Antonio Breast Cancer Symposium.