Carolyn Straehle, PhD

1
Academic Scientific Research the Importance
of Collaboration
The Story of the Breast International Group
facilitating breast cancer research
internationally
Carolyn Straehle, PhD Managing Director, BIG
2
Questions

• Why is collaboration important?
• Why should it matter to early-career
  investigators?

3
Beginnings

• Reduce the wasteful duplication of effort /
  resources
• Respond to the exponential ? in new drugs

PAST PRESENT / FUTURE
4
The Network
Founded - 1996 (Martine Piccart, Aron
Goldhirsch) - 1999 international academic
non-profit, Belgium Organization - Members 44
Research Groups - Board of Directors -
Headquarters (Jules Bordet Institute,
Brussels) - Rotating Data Centers (1
Coordinating Group/Trial) - Bordet-based
BrEAST Data Center for large registration
trials in collaboration with the Frontier
Science Technology Research Foundation
Activities 40 countries, 30 clinical
trials
5
44 Members Worldwide
EU 25 COUNTRIES Switzerland, Norway, Iceland,
Macedonia, Turkey
CANADA
Russia
ASIA-PACIFIC AUSTRALIA JAPAN NEW
ZEALAND TAIWAN China Korea Singapore
Egypt Israel
INDIA
MEXICO
BRAZIL CHILE PERU
NigeriaSouth Africa
Large multinational trials e.g. BIG 1-98, HERA,
ALTTO, MINDACT
National GROUPS or International GROUPS / centres
6
Step 1 Working with Industry
With a spirit of PARTNERSHIP!
7
Mission
Facilitating breast cancer research
internationally

• 10 Key Principles of Research Conduct
• Advance knowledge ? Serve patients
• Retain independence
• Database control / statistical leadership
• Steering Committee
• Independent Data Monitoring Committee
• Trial monitoring
• Presentations / publications academic standards
• GCP / regulatory standards
• Biological specimen collection for future
  research
• Long-term follow-up of patients

8
Mission
M. Piccart, A. Goldhirsch, W. Wood, K. Pritchard,
J. Baselga, L. Reaby, I. Kössler, S. Kyriakides,
L. Norton, A. Coates
9
Examples of BIG Research
RADIOTHERAPY
BIG 2-04 SUPREMO
SPECIAL POPULATIONS - young and elderly
BIG 3-07 DCIS
BIG 3-98 Loss of fertility survey
BIG 2-02 SOFT BIG 3-02 TEXT BIG 4-02 PERCHE
BIG 4-04 ICE BIG 1-05 CASA BIG 2-05 ACTION
OPTIMAL ENDOCRINE THERAPY
BIG 1-97 MA.17 BIG 2-97 IES BIG 1-98 Letrozole
BIOLOGICAL THERAPIES / OMICS TRIALS
CONSORTIUM
BIG 1-06 Neo-ALTTO / BIG 2-06 ALTTO
BIG 1-01 HERA BIG 3-05 TBP
BIG 3-04 MINDACT
BIG 3-04 MINDACT
BIG 1-00 p53
OPTIMAL CHEMOTHERAPY
PREVENTION
BIG 2-98 TAX-315
BIG 5-02 IBIS II
ACCELERATING DRUG AND BIOMARKER
DEVELOPMENT NeoBIG programme 2009-2014
10
BIG 1-01 HERA Design
Women with HER2 POSITIVE invasive breast cancer
IHC3 or FISH centrally confirmed
Surgery (neo)adjuvant chemotherapy (CT) ?
radiotherapy
Stratification
Nodal status, adjuvant CT regimen, hormone
receptor status and endocrine therapy, age, region
Randomization
Trastuzumab 8 mg/kg ? 6 mg/kg 3 weekly x 2 years
Trastuzumab 8 mg/kg ? 6 mg/kg 3 weekly x 1 year
Observation
11
Recruitment Exceeding all Expectations
480 sites, 39 countries
gt 20 collaborative groups
registration of trastuzumab for early bc within
5 yrs of trial start
12
Step 2 Translational Research
Large trials comparing treatments A vs B vs C
Tailored trials asking biologically relevant quest
ions
Successful transition ?

• Reinforced dialogue with basic scientists
• Reinforced dialogue with surgeons,
• pathologists, radiologists
• New models of collaboration with pharma
• Independent funding

EMPIRICAL APPROACH
TAILORED APPROACH
Retrospective Specimen collection / TR
Prospective specimen collection / TR
13
Breast Cancer Research
Coordination
Fragmentation
1996 / 1999
2004
Founding of
Better outcomes for women

• 44 research groups in 38 countries
• About 76,000 patients in about 30 studies

Founding of
14
TRANSBIG

• European Commission (FP6) Network of Excellence
• (40 partners in 21 countries)
• Some BIG groups
• Institutions known for laboratory expertise
• Small medium-sized enterprises
• EUROPA DONNA patient advocates
• European CanCer Organisation (ECCO)

Science patient treatment care
Education communication
TRANSBIG consortium managed by BIG HQ
15
M
N
i
D
A
C
T
croarray for ode Negative 1 to 3 LN
isease may void hemo herapy CLINICAL
APPLICATION OF GENOMICS (70-gene signature) FOR
IMPROVED TREATMENT TAILORING
BENEFITS Only women who NEED chemotherapy
RECEIVE it! Reduce toxicity side effects
Reduce cancer care costs Reduce burden on
health care systems
16
The Advocate

MINDACT Multidisciplinary trial
17
Step 3 Collaboration with Other Networks
NORTH AMERICA
REST OF THE WORLD
Communication Collaboration
44 non-US groups worldwide
6 NCI-sponsored clinical trials collaborative
groups
partners
Regular meetings to discuss - Shared research
priorities - Areas for collaboration -
Integration of translational research
The increased collaboration further reduces
duplication of efforts
More efficient fight against the disease
18
The ALTTO Trial
8000 women with HER2 positive breast cancer
CHEMOTHERAPY
Trastuzumab combined with lapatinib
Trastuzumab x 1y
Lapatinib x 1y
Trastuzumab ? then lapatinib
With a huge translational research effort! (e.g.
tumor / blood collection ? back to the lab!)
19
The ALTTO Trial for HER2 Positive Breast
Cancer(N 8000)
Spirit of collaboration is key!
Brussels, Jules Bordet Institute
Central Management
lead No. Am. group NCCTG (Mayo)

• Start June 2007
• 1300 hospitals
• in 49 countries

20
Recruitment Again Exceeding all Expectations
21
Step 4 Drug Biomarker Development
NeoBIG
Research program to accelerate drug biomarker
development in early breast cancer 2009 - 2014
22
Challenge No 1?
COLLABORATION!!
23
Breast Cancer Research
Fragmentation
Coordination
Integration
1996 / 1999
2004
2009 ?
2005
Active collaboration with NoAm
NeoBIG
Better outcomes for patients!
40 PARTNERS, 21 COUNTRIES
24
Some of the Issues

• Collaborative research involves academics from
  related but different disciplines as well as
  commercial partners
• Different cultures, priorities, personalities

Collaboration is not always easy and problems
arise
25
Miscommunication
Adapted from F. Cardoso
26
Difficult Negotiations
w/ permission from www.CartoonStock.com
27
Compromises
w/ Permission from www.CartoonStock.com
28
Bureaucracy
w/ Permission from www.CartoonStock.com
29
Tensions between Individuals
w/ Permission from www.CartoonStock.com
30
Resistance to Change
31
For Example

• Collaborative groups research networks must
  adapt and evolve on ongoing basis to provide
  early-career investigators with real
  opportunities for
• Professional Development
• Leadership (e.g., Principal Investigator)
• Authorship

32
But There is Progress
Fellowship opportunities, e.g., ESMO, TRANSBIG, .
Training (DNA, RNA, Pathology, biomarkers
research methodology) for early-career breast
cancer specialists
New research programs NeoBIG ...
33
Questions

• Why is collaboration important?
• Why should it matter to early-career
  investigators?

34
Why is Collaboration Important?

• Recruit patients faster, especially in niche
  populations
• Conduct essential translational research
• Answer important scientific questions more
  quickly
• Reduce or avoid duplication of efforts
• Retain scientific independence

35
Why Should it Matter?

• Provide framework within which to
• develop your own research ideas
• Seize fellowship, mentorship and networking
  opportunities
• Enrich your horizons with contacts across
  disciplines and cultures
• Develop leadership opportunities

36
And Finally
Because you can achieve really BIG things ...

• for the Common Goal
• Curing breast cancer
• Well-being of patients