Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

1. Steering Committee meeting, 24th September 2005 University of Oxford Examination Schools ATLAS Steering Committee: 24 September 2005

2. ATLAS and aTTom Update on current status adjuvant Tamoxifen Treatment: offer more? ATLAS Steering Committee: 24 September 2005

3. ATLAS and aTTom study design After several years on adjuvant tamoxifen, patient and doctor both SUBSTANTIALLY UNCERTAIN about whether to stop now or continue RANDOMISE STOP tamoxifen now CONTINUE for at least 5 more years ATLAS Steering Committee: 24 September 2005

4. Sample size sought To confirm, or refute, a 3% difference in absolute survival (e.g. 75% to 78%), 8,000 patients would have to be randomised to have a 90% chance of detecting this difference (at a 5% statistical significance level) between the two groups. To detect a 2% difference in absolute survival (e.g. 75% to 77%), 20,000 patients would be needed. ATLAS Steering Committee: 24 September 2005

5. Completion of recruitment phase in ATLAS and aTTom • January 2005: ATLAS Steering Committee (TSC) with the aTTom TSC decided to close accrual • > 20,000 women now randomised in studies of 10 vs 5 years of tamoxifen • aTTom and ATLAS closed to recruitment in March 2005. ATLAS Steering Committee: 24 September 2005

6. 12898 2354 ATLAS Steering Committee: 24 September 2005

7. 15 254 women randomised from 30+ countries: largest cancer treatment trial so far! ATLAS Steering Committee: 24 September 2005

8. Cumulative recruitment figures into aTTom by prior duration of tamoxifen ATLAS Steering Committee: 24 September 2005

9. Accrual in trials of 10 vs 5 years of tamoxifen ATLAS Steering Committee: 24 September 2005

10. Identifiers Responsible doctor Patient name Date of birth Hospital number National identification number Address Alternative contact details Clinical Date of diagnosis ER status Nodal status Recurrence (including contralateral breast cancer) Other primary cancer Menopausal status Ovarian ablation Dose of tamoxifen (daily) and prior duration Baseline data of women randomised in ATLAS: ATLAS Steering Committee: 24 September 2005

11. AGE DISTRIBUTION STOP CONTINUE ATLAS Steering Committee: 24 September 2005

12. NODAL STATUS STOP CONTINUE ATLAS Steering Committee: 24 September 2005

13. ER status ATLAS Steering Committee: 24 September 2005

14. ATLAS Older (n=2354) ER poor 9% ER unknown 68% ER positive 23% Newer (n=12898) ER poor 10% ER unknown 37% ER positive 53% Distribution of ER status in ATLAS ATLAS Steering Committee: 24 September 2005

15. Survival among women in the “older” and “newer” components of ATLAS NB: Women in STOP and CONTINUE arms combined in each component ie – this is non-randomised ATLAS Steering Committee: 24 September 2005

16. Survival in ATLAS by nodal status ATLAS Steering Committee: 24 September 2005

17. Survival in ATLAS by ER status ATLAS Steering Committee: 24 September 2005

18. ATLAS: the next few years Compliance with random allocation Completeness of follow-up At present, women with a prior duration of 4 or more years of tamoxifen before randomisation have a median follow-up of ~3 years. An absolute minimum of five more years of follow-up is needed for a proper assessment of the benefits and risks of long-term tamoxifen. ATLAS Steering Committee: 24 September 2005

19. Numbers of women where follow-up should be data available * Denominators for main breast cancer analyses H Denominators for main side-effect analyses ATLAS Steering Committee: 24 September 2005

20. Compliance in older part of ATLAS ATLAS Steering Committee: 24 September 2005

21. Compliance in newer part of ATLAS ATLAS Steering Committee: 24 September 2005

22. Completeness of follow-up data We must have up to date information on all women especially with respect to - Compliance - Recurrence - Death (and if died, date and cause of death) - Other primary cancers ATLAS Steering Committee: 24 September 2005

23. Quality of follow-up data • All forms should be completed in full! • At least 80% of the ATLAS office’s time is spent chasing follow-up queries ATLAS Steering Committee: 24 September 2005

24. Most common problems with follow-up forms • Not returned! • Not completed in full • Doctors writing “Lost to follow-up” • Dates of events missing • Cause of death not provided • Hospital admission diagnosis and date missing ATLAS Steering Committee: 24 September 2005

25. Use the information we have to help ensure long-term follow-up Identifiers Responsible doctor Patient name Date of birth Hospital number National identification number Address Alternative contact details ATLAS Steering Committee: 24 September 2005

26. SummaryLong-term follow-up and good compliance are required in ATLAS:If we can get these, we will get a reliable answer on whether longer versus shorter tamoxifen improves survival among women with early breast cancer ATLAS Steering Committee: 24 September 2005

27. ATLAS Steering Committee: 24 September 2005

28. I want to thank everyone personally for all they have done to make this collaboration work! Dr Christina Davies, ATLAS Coordinator For further information on any of this presentation, please contact atlas@ctsu.ox.ac.uk ATLAS Steering Committee: 24 September 2005