Martine J. Piccart-Gebhart, MD, PhD

1) The Breast International Group and TRANSBIG, Brussels, Belgium
(made possible by generous support from Roche)
Co-investigators: Fatima Cardoso, MD, Jules Bordet Institute; Laura van 't Veer, PhD, Netherlands Cancer Institute; Giuseppe Viale, MD, PhD, University of Milan School of Medicine; Philippe Bedard, MD Jules Bordet Institute

In February 2007 an international research network known as the TRANSBIG Consortium launched the innovative MINDACT clinical trial (Micro array In Node negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy). The goal of this trial is to determine if a new test should be used to help doctors decide upon the best treatment for women diagnosed with early stage breast cancer. This new test, known as the 70-gene signature (or MammaPrint™), analyzes the genes of a patient's tumor to see if a cancer is likely to come back (in which case treatment with chemotherapy after surgery is probably needed) or not (in which case chemotherapy can safely be avoided).

MINDACT is an ongoing complex multinational clinical trial that has been recruiting patients since March 2007 and is now recruiting about 140 patients per month. The trial had a predefined "pilot phase" consisting on the first 800 patients enrolled. This important milestone was achieved in November 2008. Since the trial is contingent upon the comparison of the 70-gene signature with the standard clinical and pathological risk factors that doctors routinely use to decide whether a patient should be treated with chemotherapy, it is important to ensure that the pathological assessment of tumor specimens is consistent across the centers participating in the study. Previous studies have shown that there may be discrepancies in the assessment of histological grading, hormonal receptor status and HER-2 protein overexpression and/or gene amplification in up to 20% of cases between different pathological laboratories.

The goal of the current study is to retest the key pathological characteristics of the first 800 patients enrolled in the trial in a high quality pathology laboratory and evaluate how discrepancies in pathological assessment with local testing may affect the underlying assumptions for the ongoing MINDACT trial. In addition, the traditional pathological assessment of key markers at the protein level will be compared with expression of the gene using a new technology known as whole genome microarray. Ultimately, the hope is that in the future doctors can reliably distinguish women with breast cancer who can be spared unnecessary chemotherapy with those who need additional therapy to prevent a recurrence of their breast cancer.

Mid-Year Progress Report:
With the present study the researchers aim at evaluating the quality of the pathologic assessment of the tumors of patients enrolled in the MINDACT trial. Ensuring high quality pathological assessment is essential to the success of the MINDACT trial, since discrepancies in pathological marker assessment may change an individual patient’s clinical risk assignment from low to high risk or vice-versa with important consequences on treatment allocation and the ultimate interpretation of the findings of the study. With the support of BCRF the central pathology review of the first 800 patients enrolled in MINDACT has started.

2) On behalf of Memorial Sloan-Kettering Cancer Center, The Breast International Group (BIG) and The Breast Cancer Intergroup of North America (TBCI)
Co-Investigators: Fatima Cardoso, MD, Institute Jules Bordet, Belgium; Julie Gralow, MD, University of Washington; Monica Morrow, MD, Memorial Sloan-Kettering Cancer Center; William C. Wood, MD, Emory University

In contrast to their female counterparts, men rarely develop breast cancer. In the US, less than 1% of all breast cancers are diagnosed in men. Doctors have a limited understanding of how to approach such an uncommon disease. Most decisions regarding treatment are based upon large clinical trials involving only women with this disease. However, there are important differences regarding the age at diagnosis, underlying risk factors, and biological characteristics which suggest that male breast cancer (Male BC) may be a distinct disease. In order to develop more appropriate treatment recommendations, a better understanding of the natural history and biology of Male BC is desperately needed. Due to the rarity of this disease, such insight can only be gained through co-operation between hospitals in different countries worldwide.

The Breast International Group, the Breast Cancer Intergroup of North America and Memorial Sloan-Kettering Cancer Center have joined forces to launch a three-part International Program on Male Breast Cancer (International Registration and Biologic Characterization Program). The first part of this Program consists of a retrospective joint analysis of a very large series of men previously diagnosed with breast cancer. This initiative will gather data regarding patient characteristics, tumor features, treatment and outcome for more than 1600 men diagnosed with breast cancer over the last 20 years. Tumor specimens (both paraffin-embedded and frozen) from a large proportion of these patients will be collected and centrally analyzed, to understand the biological characteristics of this disease and to identify important potential prognostic (indicative of the good or bad outcome of the disease) and predictive (indicative of probability of response to certain therapies) markers, which will then be validated in the third part of the Program.

This important study will provide invaluable information regarding the behavior of this rare disease and, combined with the information gathered during the second part of the Program (an international Male BC registry), will form the basis and rationale for the design of an international Male BC clinical trial.

During the past year, the preparatory work needed to launch this study has been done. The full protocol and the selection of centers have been accomplished. The database for collection and analysis of both clinical and pathological data is in advanced stages of development. The central labs have started developing common protocols for the construction of TMAs, for the analysis of the different biomarkers and for the reporting of the results. The researchers plan to have centers/groups active by July and to start the collection of data and material by the fall 2009 and they are aiming at finalizing the central pathology review by the end of 2009.

Mid-Year Progress Report:
During this period the preparatory work needed to launch this study has been done. The full protocol and database development for collection and analysis of both clinical and pathological data are finished. The central labs have developed common protocols for the construction of tissue microarrays (TMAs), for the analysis of the different biomarkers and for the reporting of the results. The participant centers/groups were selected and the activation process started. The researchers plan to start the actual collection of data and tumor samples in February and are aiming at finalizing the central pathology review by the mid of 2010. The objective is to analyze the first results of the retrospective male breast cancer (Male BC) study in 2010 as well as present it in an international conference and to prepare a manuscript for publication in a peer reviewed journal. In parallel, they are continuing their efforts to obtain the much needed funds for the associated correlative translational research projects. To this end, additional grant applications will be made by the study coordinators and two central pathologists.

Bio:
Dr. Piccart earned her MD and PhD at the Université Libre de Bruxelles, Belgium, and received her oncology qualifications in New York and London. She is a member of the "Académie Royale de Médecine de Belgique".

With a primary interest in breast cancer and drug development, Dr. Piccart has a strong interest 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 Brussels-based Breast International Group (BIG), created in 1996 to facilitate international breast cancer clinical trials, and TRANSBIG, a European Commission supported translational research consortium to complement BIG's clinical research network. BIG brings together 44 collaborative groups from around the world and has over 30 trials under its umbrella; TRANSBIG represents 39 institutions in 21 countries; and BIG has recently launched an innovative biomarker and drug development program focused on neo-adjuvant trials, called NeoBIG.

Dr. Piccart is an active member of many professional organizations, currently serving as president-elect of the European Society for Medical Oncology (ESMO). She is immediate past-president of the European Organization for the Research and Treatment of Cancer (EORTC) and recently served on the American Society of Clinical Oncology (ASCO) Board.

She is author or co-author of more than 300 scientific publications in peer-reviewed journals and has received numerous prestigious awards for her contribution to research in oncology, including the ESMO Award for Exceptional Contribution to the Advancement of Medical Oncology in Europe (1997), a "Jacqueline Seroussi Memorial Foundation for Cancer Research Award" for "International leadership in translational and clinical research that has improved treatment outcomes for women with early stage and advanced breast cancer" (2005), the 14th Claude Jacquillat Award for achievements in clinical oncology (2006) and the ESMO-GSK Lifetime Achievement Award in Breast Cancer Research (to the Breast International Group in 2006). She was awarded the "Miami Breast Cancer Conference Award of Excellence for 2007" and the Jill Rose Award for distinguished biomedical research in October 2009 in New-York. More recently, Dr Piccart received the William L. McGuire Award in recognition of her contribution in breast cancer research in December 2009 in San Antonio.