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 permissionBIG-TRANSBIG HQ– Used with permission

TRANSLATING MOLECULAR KNOWLEDGEINTO EARLY BREAST CANCER MANAGEMENT

Fatima Cardoso, MDTRANSBIG Scientific Director

BIG-TRANSBIG HQ– Used with permissionBIG-TRANSBIG HQ– Used with permission

BREAST CANCER RESEARCH IN EUROPEBREAST CANCER RESEARCH IN EUROPE

FragmentationFragmentation Coordi nationCoordi nation

Founding Founding of the of the

Breast International GroupBreast International Group(BIG)(BIG)

19961996

• 44 research groups in 38 44 research groups in 38 countriescountries

• Over 76,000 patients in Over 76,000 patients in >30 studies>30 studies

Better Better outcomes for outcomes for

womenwomen

TRANSBIGTRANSBIG

20042004

BIG-TRANSBIG HQ– Used with permission

TRANSBIGTRANSBIG

Structure: FP6 Network of Excellence since 2005

Aim: To integrate, strengthen and facilitate translational and clinical breast cancer research

1st project: MINDACT clinical trial

EU fundingOther

Biotechnology Companies (Agendia)

Pharmaceutical IndustryNational Resources

Other Grants

EUEU

Tumor samples of known clinical outcome

No distant metastasesgroup

Unbiased full genome gene expression

analysis

Distant metastasesgroup

70 prognosis genes

Tu

mo

r s

amp

les

Metasta

ses: wh

ite=

+

Prognosis reporter genes

Development of 70 geneexpression 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. 2002

Courtesy & adapted from L van ‘t Veer

BIG-TRANSBIG HQ– Used with permission

Development of 70-gene

prognostic signature

(MammaPrint ™)

STEP 1STEP 1

IndependentIndependentvalidation study on validation study on

archive materialarchive material

STEP 2STEP 2

MINDACT trial

STEP 3STEP 3

Levels of evidence for biomarker studies

E.U. GRANT, 6E.U. GRANT, 6thth Framework Programme Framework Programme

A 3-STEP PROJECT A 3-STEP PROJECT

BIG-TRANSBIG HQ– Used with permissionBIG-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 permissionBIG-TRANSBIG HQ– Used with permission

Evaluate Clinical-Pathological risk and 70-gene signature risk

both HIGH riskDiscordant

cases

both LOW risk

Use Clin-Path risk or the 70-gene signature to decide Chemo or not

55% 32% 13%

R-T

ChemotherapyNo chemotherapy

EORTC 10041 BIG 3-04 trial MINDACT TRIAL DESIGN6,000 Node - & 1-3 N+ women

Potential CT sparing in 10-15% pts

Good signatureLow risk

Poor signatureHigh 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

BIG-TRANSBIG HQ– Used with permission

MINDACT RECRUITMENT

As of 01.03.2009

Screened: 2225 ptsEnrolled: 1208 pts

BIG-TRANSBIG HQ– Used with permissionBIG-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 RESEARCHA GOLD MINE FOR RESEARCH

Independent biological materials bankPolicy for access to samples and/or data

BIG-TRANSBIG Secretariat– Used with permissionBIG-TRANSBIG Secretariat– Used with permission

Applicants deadline APRIL 15

Interviews for applicants selection April-May

July 2008- Confidential

ACKNOWLEDGEMENTS ACKNOWLEDGEMENTS --11

BIG-TRANSBIG Team EORTC MINDACT Team

ALL TRANSBIG PARTNERS

ALL PATIENTS

BIGBIG--TRANSBIG SecretariatTRANSBIG Secretariat–– Used with permissionUsed with permissionMarch 2009March 2009 -- ConfidentialConfidential

((££49.000) 62.50049.000) 62.500UKUK

200.000200.000Dutch Cancer Society (KWF)Dutch Cancer Society (KWF)

250.000250.000FondationFondation ContreContre le Cancer (BELGIUM)le Cancer (BELGIUM)

103.074103.074Jacqueline Jacqueline SeroussiSeroussi Memorial FoundationMemorial Foundation

101.630101.630Susan G. Komen for the CureSusan G. Komen for the Cure

400.000400.000EBCCEBCC--Breast Cancer Working Group Breast Cancer Working Group -- asblasbl

540.000540.000Breast Cancer Research FoundationBreast Cancer Research Foundation

10.000.00010.000.000Agendia**Agendia**

50.00050.000Association Le cancer du sein, parlonsAssociation Le cancer du sein, parlons--en!en!

187.234187.234Veridex LLCVeridex LLC

240.000240.000Eli LillyEli Lilly

2.812.3502.812.350SanofiSanofi--Aventis GroupAventis Group

7.667.1657.667.165F. HoffmannF. Hoffmann--La RocheLa Roche

11.000.00011.000.000NovartisNovartis

7.000.0007.000.000European CommissionEuropean Commission

(EUR)(EUR)Fund providerFund provider

** Agendia’s investment is in services provided and not direct funds

ACKNOWLEDGEMENTS ACKNOWLEDGEMENTS –– 2: FUNDING2: FUNDING

Brussels Breast Cancer Walk-Run & American Women’s Club of BrusselsBIG-TRANSBIG HQ– Used with permissionBIG-TRANSBIG HQ– Used with permission