1. The IBCSG August 2007

2. History of IBCSG

3. In January 1976, Dr Jan Stjernswärd invited: Kurt Brunner, John Forbes, Percy Helman, Carl- Magnus Rudenstam, Ken Stanley, Martin Tattersall, John Simpson and Marvin Zelen Soon joined by: Alan Coates, John Collins, Franco Cavalli, Jurij Lindtner, Ian Russel, Hans-Jörg Senn, Aron Goldhirsch & Rich Gelber

4. History of IBCSG  The Ludwig Breast Cancer Study Group (LBCSG) was founded in 1977 In 1976 an enthusiastic researcher, Dr Jan Stjernswärd, invited a group of friends to create an international collaborative group dedicated to clinical research…

5. The Goals of IBCSG

6. Goals The IBCSG conducts academic trials in early breast cancer The IBCSG is dedicated to innovative clinical cancer research designed to improve the outcome of women with breast cancer The IBCSG has been and continues to be a pioneer in research into combined hormonal therapy and chemotherapy, timing and duration of adjuvant therapies and quality of life of breast cancer patients.

7. The Structure and Organization of IBCSG

8. IBCSG: The Organization Foundation under Swiss law Foundation Council (President: Prof. Beat Thürlimann) Scientific Committee (Co-Chairs: Prof. Aron Goldhirsch and Prof. Alan Coates) CEO (Prof. Monica Castiglione)

9. IBCSG: The Structure Participants all over the world Coordinating Center, Bern Data Management Center, Amherst Statistical Center, Boston Pathology office, Milan & Glasgow Quality of Life office, Bern Data Safety & Monitoring Committee IBCSG Ethics Committee

12. Global cooperation

13. A worldwide collaboration

14. Australia Belgium Brazil Canada Chile Hungary Russia Slovenia South Africa Spain Sweden Switzerland United Kingdom India Italy New Zealand Nigeria Peru Romania

15. IBCSG: What is special? The “red line” of research questions Investigation of long-term biological principles Quality control by long-term follow- up Logistical and high intellectual visibility

16. High quality clinical research Data manager and medical review of each case Auditing Institution evaluation Safety control: SAE reportingSAE reporting Pathology central review 10_Pathology material submission.ppt10_Pathology material submission.ppt Banking Pioneer work in Quality of Life questions IBCSG Strengths

17. Accrual

18. Some numbers ~ 1’000 new patients per year > 22’000 patients entered overall > 15’000 patients in follow up

19. Entry and Follow-up through 2006

20. Publications The IBCSG published 187 papers up to June 19, 2007. 21 studies are published

21. Clinical Trials

22. Open studies IBCSG 22-00 IBCSG 23-01 IBCSG 24-02 »SOFT » IBCSG 25-02 « TEXT » IBCSG 27-02 IBCSG 29-03 IBCSG 31-03 « IBIS II » IBCSG 32-05 « CASA » IBCSG 33-03 IBCSG 34-05 (SWOG 0230) IBCSG 35-07 « SOLE » IBCSG 36/37-07 « (Neo)ALTTO »

23. IBCSG 22-00 Trial22.ppt Trial22.ppt Endocrine Non-Responsive Disease Strata Menopausal Status Type of CT Institution After definitive surgery but within 56 days after the first day of the last cycle of induction CT CT* CT*  CM x 12 mos. *Approved Induction CT Regimens RANDOMIZE Study Chair: Marco Colleoni

24. IBCSG 23-01 Patients with clinically node negative breast cancer (< 3 cm) and micrometastases (< 2 mm) in the sentinel node Axillary Dissection vs. No Axillary Dissection Study Chair: Viviana Galimberti

25. IBCSG 23-01:Sentinel lymph node Trial SentinelNodeBiopsy NegativeNo further surgery No further surgery Micro < 2mm Axillary dissection Micro > 2mmAxillary dissection Random T < 3 cm N 0 M 0

26. IBCSG 23-01 Status Activated for EIO : April 2001 Group activation: December, 2001 Amendment 1: September, 2002 Amendment 2: June 2007 Accrual (30June2007) = 590 Target = 1960

27. Tailored Treatment Investigations IBCSG 24-02, 25-02, 26-02 Global Participation: BIG and North American Intergroup and …

28. Tailored Treatment Investigations Premenopausal patients with endocrine- responsive disease (ER > 10% and/or PgR > 10%) 24-02 Suppression of Ovarian Function Trial (SOFT) 25-02 Tamoxifen and Exemestane Trial (TEXT)

29. IBCSG 27-02 (BIG 1-02) Adjuvant Chemotherapy for Radically Resected Loco-Regional Relapse Observation +/- RT(  HT for HR+)+) CT +/- RT (  HT for HR+) CT=chemotherapy; HT=hormone therapy; RT=radiotherapy HR+=ER+ and/or PgR+ RANDOMIZERANDOMIZE SURGERYSURGERY Study Chair: Stefan Aebi Strata -Prior CT -ER+ and/or PgR+ -Location of recurrence

30. IBCSG 27-02 (BIG 1-02) Final protocol approved by Ethical Committee: March, 2002 Activated July 2002 Accrual by 30.June2007 = 99 Targeted accrual = 1960

31. IBCSG 29-03 (BIG 03-98) A Survey to assess the attitude of patients aged less than 35 years, with early breast cancer, towards the risk of loss of fertility related to adjuvant therapies

32. IBCSG Trial 32-05/BIG 1-05 Chemotherapy Adjuvant Studies for women at advanced Age (CASA) Phase III Trials Evaluating the Role of Adjuvant Caelyx® for Women (age 66 years or older) with Endocrine Nonresponsive Breast Cancer Who Are NOT Suitable for being offered a “Standard Chemotherapy Regimen”

33. IBCSG 33-03 A randomized controlled trial of a consultation skills training package for doctors, concerning communication of oncologists about standard treatment options and clinical trials with patients with early breast cancer.

34. IBCSG 34-05 (SWOG 0204) LHRH Analog during chemotherapy to reduce ovarian failure premenopausal women (age >18 - < 50) receptor negative, completely resected pT1-pT3; pSN0, pN0-pN2; M0 Adjuvant or neoadjuvant CT planned RT allowed Rando within 84 days after final surgery Target accrual: 416 patients over 3 years

35. IBCSG 34-05 (SWOG 0204) RANDOMIZERANDOMIZE Standard CT Goserelin (Zoladex) plus standard CT Stratify: Age <40 vs. 40 – 49) Chemotherapy regimen: - 4 cycle anthracycline based vs. - 6 – 8 cycle anthracycline based vs. - 6 – 8 cycle non anthracycline based

36. A phase III trial evaluating the role of continuous letrozole versus intermittent letrozole following 4 to 6 years of prior adjuvant endocrine therapy for postmenopausal women with hormone-receptor positive, node-positive early stage breast cancer. IBCSG 35-07 S LE

37. RANDOMIZATION Design 1 Without Taxane* LVEF  50 M Piccart, EA Perez *mainly out of TBCI sites Radiotherapy as indicated concomitant with HER2 directed therapies Lapatinib 1 yr Trastuzumab Weekly 12 weeks lapatinib 7.5 mo 3-weekly trastuzumab Lapatinib + 3-weekly trastuzumab 1 year 6 weeks break IBCSG 36-07/BIG2-06 (ALTTO ) HER2+ invasive breast cancer Surgery, complete (neo)adjuvant anthracycline-based chemotherapy Centrally-determined HER2+