BIG-TRANSBIG HQ– Used with permission TRANSLATING MOLECULAR KNOWLEDGE INTO EARLY BREAST CANCER MANAGEMENT Fatima Cardoso, MD TRANSBIG Scientific Director

BIG-TRANSBIG HQ– Used with permission BREAST CANCER RESEARCH IN EUROPE Fragmentation Coordi nation Founding of the Breast International Group (BIG) research groups in 38 countries 44 research groups in 38 countries Over 76,000 patients in >30 studies Over 76,000 patients in >30 studies Better outcomes for women TRANSBIG 2004

BIG-TRANSBIG HQ– Used with permission TRANSBIG Structure: FP6 Network of Excellence since 2005 Aim: To integrate, strengthen and facilitate translational and clinical breast cancer research 1st project: MINDACT clinical trial Biotechnology Companies (Agendia) Pharmaceutical Industry National Resources Other Grants EU

Tumor samples of known clinical outcome No distant metastases group Unbiased full genome gene expression analysis Distant metastases group 70 prognosis genes Tumor samples Metastases: white=+ Prognosis reporter genes Development of 70 gene expression profile Good signature Poor signature ~4% die of breast cancer ~96% survive breast cancer ~50% die of breast cancer ~50% survive breast cancer N Engl J Med, Vol 347 (25), Dec Courtesy & adapted from L van t Veer

BIG-TRANSBIG HQ– Used with permission Development of 70-gene prognostic signature (MammaPrint ) STEP 1 Independent validation study on archive material STEP 2 MINDACT trial STEP 3 Levels of evidence for biomarker studies E.U. GRANT, 6 th Framework Programme A 3-STEP PROJECT

BIG-TRANSBIG HQ– Used with permission AIM: Give BC patients a tailored treatment approach by better identifying who needs chemotherapy and who can be safely spared Only women who NEED chemotherapy RECEIVE it! BENEFITS: Reduce toxicity & side effects Reduce cancer care costs Reduce burden on health care systems croarray for ode Negative & 1 to 3 + LN isease may void hemo herapy

BIG-TRANSBIG HQ– Used with permission Evaluate Clinical-Pathological risk and 70-gene signature risk both HIGH risk Discordant cases both LOW risk Use Clin-Path risk or the 70-gene signature to decide Chemo or not 55% 32%13% R-T Chemotherapy No chemotherapy EORTC BIG 3-04 trial MINDACT TRIAL DESIGN 6,000 Node - & 1-3 N+ women Potential CT sparing in 10-15% pts

Good signature Low risk Poor signature High risk The Surgeon The Basic Researcher The Medical Oncologist The Radiotherapist The (research) Nurse The Pathologist The Radiologist The Patient The Advocate … MINDACT: Multidisciplinary trial

BIG-TRANSBIG HQ– Used with permission

MINDACT RECRUITMENT As of Screened: 2225 pts Enrolled: 1208 pts

BIG-TRANSBIG HQ– Used with permission FROZEN TUMOR SAMPLES (remaining after RNA extraction for the MINDACT trial) PARAFFIN-EMBEDDED TUMOR SAMPLES (after TMA construction) SERUM & BLOOD SAMPLES FOR FUTURE RESEARCH A GOLD MINE FOR RESEARCH Independent biological materials bank Policy for access to samples and/or data

BIG-TRANSBIG Secretariat– Used with permission Applicants deadline APRIL 15 Interviews for applicants selection April-May

BIG-TRANSBIG HQ– Used with permission