Fatima Cardoso, MD

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

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.

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: Julie Gralow, MD, University of Washington; Monica Morrow, MD, Memorial Sloan-Kettering Cancer Center; Martine J. Piccart-Gebhart, MD, PhD, Jules Bordet Institute, Beldium; 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.

Bio:
Dr Fatima Cardoso finished Medical School in 1992 in University of Porto, Portugal and her specialty in Medical Oncology (Board certification) in July 2000 at the Portuguese Institute of Oncology - Porto Center, Portugal. From November 2000 to October 2002, she worked at the Translational Research Unit of the Jules Bordet Institute-Brussels (Prof Martine Piccart), as a Clinical and Translational Research Fellow, supported by an educational grant from the "Université Libre de Bruxelles". From November 2002 to August 2003, she worked at the Department of Molecular and Cellular Oncology of the MD Anderson Cancer Center, Texas, USA (Prof Mien-Chie Hung) as a Basic Research Fellow, supported by an educational grant from the MD Anderson Cancer Center and from the "Fonds Jean-Claude Heuson"- Belgium. Since October 2003, she has been an Assistant Professor at the Medical Oncology Clinic of the Jules Bordet Institute, Brussels, Belgium, where besides her clinical work, she is an active member of the Translational Research Unit, she is responsible for phase II-III trials in breast cancer, and is the Scientific Director of the TRANSBIG network. She is also board certified in Internal Medicine since October 2004.

Dr Cardoso's research interests include the biology of breast cancer, predictive markers of response to systemic therapy and new anti-cancer agents. Dr Cardoso is a member of EORTC-BCG, ASCO, AACR, WICR, ESMO, EACR, and Co-founder & former Vice-President of the "Flims Alumni Club (FAC)" (a multidisciplinary European network of young cancer specialists). She is also a member of the prestigious group "Innovators in Breast Cancer".

She has been invited to give lectures in several national and international meetings, she is a member of the faculty of the FECS/AACR/ASCO Flims Workshop on "Methods in Clinical Cancer Research", and the responsible professor of the subject "Research in Oncology" of the Master in Oncology of the Portuguese Institute of Oncology-University of Port, Portugal. She is also a member of the School of Oncology-European Breast Cancer Conference Task Force for the development of guidelines for Metastatic Breast Cancer. She is an associated/specialty editor for The Breast, EJC and "Le Journal du Réseau Cancer de l'Université Libre de Bruxelles", and member of the editorial board of several other Journals. She presently has 109 publications (41 as first/last author) and twelve book chapters.

She had received several educational and research grants from the European Society of Medical Oncology (ESMO), the Federation of European Cancer Societies (FECS), the Portuguese League Against Cancer, the Portuguese Ministry of Health, the Free University of Brussels, the "Fonds Jean-Claude Heuson", the Fondation Lambeau-Marteau, the Belgian Federation against Cancer, and the European Union Framework VI Programme.