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 early 2007 the TRANSBIG Consortium, an international research network, launched the MINDACT clinical trial, which is testing a new strategy to individualize treatment for women with breast cancer. The goal of this trial is to assess the usefulness of a 70-gene signature (commercialized under the name of MammaprintTM) in determining the best treatment for women with breast cancer after their breast cancer has been surgically removed.

Developed by a member of the TRANSBIG Consortium, the Netherlands Cancer Institute, this 70-gene signature is a tool that can analyze genes in a patient's tumor and determine whether 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). Today, women whose cancer has spread to the surrounding lymph nodes are thought to be at higher risk for having their cancer return and are often treated with chemotherapy after their cancer has been removed. Previously, the 70-gene signature had only been validated in women whose cancer had not spread to their lymph nodes, and women with lymph node involvement were excluded from participating in MINDACT.

Since receiving a BCRF grant in October 2007, the TRANSBIG Consortium has demonstrated that the 70-gene signature can also be used to identify patients whose cancer involves 1 to 3 lymph nodes but have a low risk of recurrence. As a result, the MINDACT trial now includes women with 1 to 3 involved lymph nodes. Traditionally, women who are 70 years of age or older with breast cancer have not been allowed to participate in clinical trials studying new tests and treatments. So far, the 70-gene signature has only been tested in women less than 70 years of age, and the MINDACT trial does not allow older women to participate.

With continued support from the BRCF, TRANSBIG will be able to finalize testing the utility of the 70-gene signature in predicting the risk of relapse in elderly women diagnosed with breast cancer, which may lead to the inclusion of these patients in MINDACT. Ultimately, the hope is that doctors may use the 70-gene signature in the future to better identify women with breast cancer, regardless of lymph node involvement and age, who can be spared unnecessary chemotherapy following the surgical removal of their tumor.

Until now, it was thought that all HER-2 positive breast cancer patients needed adjuvant chemotherapy in addition to adjuvant trastuzumab and adjuvant endocrine therapy (if the hormonal receptors are positive). However, recent data seem to show that this population is quite heterogeneous. Using the 70-gene signature, for example, a significant proportion of women with HER-2 positive disease are predicted to have a low risk of recurrence. Hence, it may also be possible to safely spare these patients adjuvant chemotherapy, if these results are confirmed.

With the support of BCRF, the purpose of this study is to confirm that HER-2 positive breast cancer is heterogeneous and can be sub-divided into two subgroups with different prognosis as defined by the 70-gene signature, and can therefore be treated differently. The second step will be to characterize in detail the biology of these subgroups, using different available technologies, to better define the best treatment strategy for each.

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 women, 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.

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.