Fatima Cardoso, MD

2009-2010 BCRF Projects:

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.

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: 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.

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. Fatima Cardoso attended medical school at the University of Porto and completed her specialization in medical oncology (board certification) in July 2000 at the Portuguese Institute of Oncology, Porto Center, Portugal. In 2004 Dr. Cardoso also obtained board certification in internal medicine. Dr. Cardoso has completed two research fellowships, one at the Translational Research Unit of the Jules Bordet Institute, Brussels, Belgium (Prof. Martine Piccart), and another at the Department of Molecular and Cellular Oncology of the MD Anderson Cancer Center, Texas, USA (Prof. Mien-Chie Hung). These research fellowships were sponsored by educational grants from the Université Libre de Bruxelles and the MD Anderson Cancer Center and from the Fonds Jean-Claude Heuson of Belgium, respectively. Her main research interests include biology of breast cancer, prognostic and predictive markers of response to systemic therapy and new anticancer agents.

From October 2003 to June 2010, Dr. Cardoso was an Assistant Professor at the Medical Oncology Clinic of the Jules Bordet Institute, where, besides her clinical work, she was active in the Translational Research Unit and was responsible for phase II-III trials in breast cancer. From October 2010 she will take the position of Head of Breast Cancer Unit at the newly created Champalimaud Cancer Center in Lisbon, Portugal. Dr. Cardoso is also the Scientific Director of the TRANSBIG consortium, and co-Principal Investigator of the MINDACT trial, TRANSBIG's main project. In 2009, she became the coordinator of the Breast Cancer Program for the European School of Oncology (ESO), and co-chair, with Dr. Eric Winer, on the ESO Task Force for the development of international guidelines for metastatic breast cancer.

Dr. Cardoso is a professor of the Master in Oncology program of the Portuguese Institute of Oncology, University of Porto, Portugal. She is co-editor-in-chief of The Breast Journal, associate editor of the European Journal of Cancer and a member of the editorial board of several other journals. Dr. Cardoso is the author of over 230 publications and in addition she has 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, the Breast Cancer Research Foundation, the Susan G. Komen Foundation, and the European Union Framework VI Programme.